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1

Harrington, Lauriane. "The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066328/document.

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Le tabac est consommé par environ un milliard de personnes. D'après l'Organisation Mondiale de la Santé, le tabagisme est la première cause évitable de mortalité dans le monde, provocant six millions de morts par an. La nicotine est le composant neuro-actif principal dans le tabac, et exerce ses effets neurologiques via une activation directe des récepteurs nicotiniques de l’acétylcholine (nAChR). Ces récepteurs transmembranaires sont composés de sous-unités alpha, ou alpha plus beta, créant une variété de canaux ioniques ligand-dépendants activés par le neurotransmetteur ACh. Les études génétiques chez l’homme ont mis en évidence des variants dans le cluster génomique CHRNA5-CHRNA3-CHRNB4, codant pour les sous-unités α5, α3 et β4, comme facteurs influençant le tabagisme. Cette thèse a étudié le rôle des nAChRs contenant la sous-unité β4 (β4*) dans l’addiction à la nicotine. En collaboration, nous avons montré que les souris déficientes pour la sous-unité β4 (β4 KO), sont moins sensibles aux effets récompensant et aversifs de la nicotine. En générant un lentivirus exprimant la séquence murine d'ADN complémentaire de β4, j’ai pu restaurer son expression dans des régions d’intérêt du cerveau, sur un fond génétique β4KO. Ceci a permis de mettre en évidence le rôle du réseau habénulo-interpedonculaire dans la contribution des β4* nAChRs à la consommation de nicotine. Ceci a également démontré le rôle modulateur de ces récepteurs dans les réponses de la voie mésolimbique à la nicotine, voie centrale dans l'effet renforçant des drogues
Tobacco is consumed by an estimated 1 billion people world-wide. The World Health Organization names tobacco consumption the primary cause of preventable morbidity and mortality, causing six million deaths per year. Nicotine is the principal neuro-active compound in tobacco, and exerts neurological effects by binding to nicotinic acetylcholine receptors (nAChRs). These transmembrane receptors are composed of alpha or alpha plus beta subunits, forming a diverse variety of ligand-gated ion channels endogenously activated by ACh. Human genetic studies have highlighted variants in the CHRNA5-CHRNA3-CHRNB4 genomic cluster, coding for subunits α5, α3 and β4, as altering smoking behaviours. The present thesis investigated the role of β4-containing (β4*) nAChRs in nicotine addiction. In collaboration, we showed that β4 knockout (KO) mice are less sensitive to nicotine reward and nicotine aversion. Generating a lentivirus for the expression of mouse β4 nAChR subunit complementary DNA, I was able to restore receptor expression to brain regions of interest on a KO background, locating the role of β4* nAChR in nicotine reward and aversion to the habenulo-interpedunular pathway. This also demonstrated the receptor’s modulation of nicotinic responses of the mesolimbic system, central hub of drug reinforcement
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2

Keyworth, Helen. "Nicotine addiction : behavioural and neurochemical mechanisms." Thesis, University of Surrey, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.606818.

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Few attempts "to quit smoking are successful, making current interventions relatively ineffective. Evidence shows that exercise decreases nicotine withdrawal symptoms in humans, but the mechanism is unclear. Part of this thesis aimed to explore the mechanisms underpinning the effect of exercise on nicotine withdrawal in both human and animal models of nicotine addiction. The role of perception of exercise intensity was investigated in temporarily abstinent smokers. Perceived and objective moderate intensity exercise and passive waiting all reduced withdrawal symptoms, and salivary cortisol was attenuated compared with pre*abstinence levels, but there was no difference between any of the interventions. These results indicate that exercise may reduce withdrawal by acting as a distraction, but does not preclude biochemical mechanisms from playing a role. Nicotine-treated mice undertaking 2 or 24 hrs/day running wheel access, demonstrated reduced mecamylamine-precipitated withdrawal symptoms compared with sedentary mice, indicating that even a low level of exercise aids in reducing withdrawal symptoms. This was accompanied by a significant increase in hipp05ampal 0.7 nicotinic receptors (nAChRs), implicating the α7 nAChR in a mechanism underlying the effect of exercise in nicotine withdrawal. The effect of nicotine on nAChR and oxytocin receptor (OTR) binding in a mouse model of schizophrenia was investigated using mice with a G72 protein insertion (G72Tg). Nicotine reversed social cognitive deficits in G72Tg mice, associated with attenuation of α7 nAChR and OTR binding in the cingulate cortex by nicotine in G72Tg mice. These results implicate both α7 nAChRs and OTR as targets for the development of pharmacotherapies for the treatment of social and cognitive deficits in schizophrenia. All toghether, the results in this thesis show that the α7 nAChR may be involved in modulating behavioural responses in nicotine addiction. Furthermore, dysregulation of α7 and OT receptors may underlie the mechanism of cognitive and social deficits in schizophrenia.
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3

Pashmi, Ghazaleh. "Immunotherapy approach to combat nicotine addiction." Thesis, University of Bath, 2004. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419340.

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Smoking is now recognized as the single largest avoidable cause of premature death and disability in Britain and probably the greatest avoidable threat to public health worldwide. There are several therapies available to combat nicotine addiction ranging from psychological therapy to pharmacological interventions such as Nicotine Replacement Therapy. However, success rates for these therapies individually and mixture of therapies together, are still low and can be improved. A new strategy in helping quit rates is immunotherapy. This research project has focused on targeting cotinine, the major metabolite of nicotine, to produce a vaccine as a cessation method. The effect of cotinine on nicotine-evoked dopamine release was first examined using 96-well plate assay in chapter 2. Cotinine was shown to decrease nicotine - evoked dopamine release, probably by desensitising the nAChRs. a6p2*, a4p2 receptor subtypes were implicated, using competitive antagonists. Trans-4-thiol cotinine was produced as a viable derivative and conjugated to ovalbumin in the appendix and chapter 3. Vaccination of rats generated anti-cotinine antibodies, although mid-point titres were low. Improvements were made in chapter 4 which increased the mid-point antibody titres. The improvements included change of carrier molecule to Tenatus Toxoid, allowing for 15 derivative attachments per carrier molecule, and change of adjuvant. The best concentration of conjugate to be used in vaccination was determined to be 5 pg which produced specific antibodies towards cotinine. Blood nicotine and cotinine concentrations after chronic nicotine treatment showed vaccination resulted in the retention of cotinine in the blood, presumably reducing the concentration reaching the brain, in chapters 4 and 5. Similar results were also obtained after acute nicotine treatment in chapter 5. The effect of vaccination on nicotine - evoked dopamine release was studied in chapters 4 and 5; an increase in nicotine-evoked dopamine release was observed in vaccinated animals. This suggests the retention of cotinine in the blood and the consequent reduction of antagonism of the actions of nicotine by cotinine, allowed nicotine to have a larger effect. Nicotineinduced locomotor activity was not affected by vaccination, however future work is needed to give conclusive results. These results have provided preliminary proof of concept for this immunotherapy approach. Future in vivo experiments will elucidate the actions of this vaccine on addiction mechanisms and facilitate the development of this approach as a therapy to help people overcome nicotine addiction.
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4

Saravia, Santos Rocio 1988. "Novel insights in nicotine addiction : focus on cognitive function." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/665841.

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Cigarette smoking continues to be leading cause of preventable cause of death worldwide. Cognitive modulation by nicotine seems to be a key factor in nicotine addiction. Several studies indicate that initial nicotine intake has a positive effect on cognition, which may contribute to the development of nicotine dependence. Conversely, when chronic nicotine treatment ceases, cognitive functioning is altered. The orexin and the endocannabinoid system have been reported to play a crucial role in different stages of nicotine addiction and in learning and memory processes. Our results show that orexin receptors influence the pro-cognitive effects of acute nicotine treatment, whereas the endocannabinoid system acting through CB1R modulates the cognitive deficits associated with nicotine withdrawal. In addition, our work reveals an inflammatory process associated with the cognitive deficits of early nicotine abstinence. Given that the presence of cognitive alterations is associated with increased smoking relapse risk, our results identify CB1R and anti-inflammatory drugs as new potential therapeutic strategies for nicotine dependence.
El consumo de cigarrillos es una de las principales causas de muerte prevenible en el mundo. Los efectos de la nicotina sobre la memoria parecen parece ser un factor clave en la adicción a la nicotina. Diversos estudios indican que el consumo inicial de nicotina tiene un efecto positivo sobre la cognición, lo que puede contribuir al desarrollo de la dependencia de la nicotina. Por el contrario, cuando el consumo de nicotina cesa, se altera el funcionamiento cognitivo. Las orexinas y el sistema endocannabinoide desempeñan un papel crucial en las diferentes etapas de la adicción a la nicotina y en los procesos de aprendizaje y memoria. Nuestros resultados demuestran que los receptores de orexina la mejora de memoria inducido por un el tratamiento agudo de nicotina, mientras que el sistema endocannabinoide, actuando a través de los receptores CB1 modula los déficits cognitivos asociados con la abstinencia de nicotina. Además, hemos revelado que un proceso inflamatorio está asociado al desarrollo de los déficits cognitivos de la abstinencia a nicotina. Dado que la presencia de alteraciones cognitivas se asocia con un mayor riesgo de recaída en el hábito de fumar, nuestros resultados identifican a los receptores CB1 y fármacos antiinflamatorios como potenciales nuevas estrategias terapéuticas para la dependencia de la nicotina.
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5

Kolokotroni, Katerina Zoe. "Nicotine addiction and impulsive behaviour : disentangling the relationship." Thesis, University of Leeds, 2007. http://etheses.whiterose.ac.uk/679/.

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Drug addiction can now be considered a global epidemic with considerable psychological, physical, social and economicc osts. Substantial research remains focused upon furthering our understating of the disorder, for which current treatments are limited in their effectiveness. More recently there has been an increased interest in the multidimensional construct of impulsivity and its association with addiction. Impulsivity is a hallmark feature of drug addiction, with drug users frequently displaying a preference for immediate over delayed gratification (impulsive choice) and a loss of inhibitory control (disinhibition) (Madden et al.,1997). To date, our understanding of the complex association between impulsivity and drug addiction has been hindered by the cross sectional nature of the majority of research conducted. As a result of this it has been unclear whether impulsivity is a risk factor or a consequence of drug abuse. The experiments of this thesis were primarily concerned with exploring the latter of these theories, in the hope of elucidating the role of drug induced impulsivity in the establishment maintenance and relapse of drug dependence. This was achieved by exploring the effects of nicotine in two animal paradigms of impulsivity; the delayed reward paradigm which assessed impulsive choice,and the symmetrically reinforced go/no-go visual discrimination task which measured behavioural disinhibition. A series of preliminary experiments confirmed the suitability of both tasks for exploring the relationship between impulsivity and nicotine dependence. Behavioural disinhibition in the go/no-go task was stable, lacked sensitivity to changes in primary motivation and furthermore appeared not to be dependent on timing mechanisms. Impulsive choice in the delay discounting task was stable and delay sensitive. Whilst decreasing primary motivation was without effect on impulsive choice, increasing motivation for food reward was found to reduce levels of impulsivity. Acutely, nicotine increased both disinhibition (0.5mg/kg,s .c .) and impulsive choice (0.125,0.25,0.5mg/kg,s .c .). The acute effects of nicotine on both components of impulsivity were effectively antagonised by the centrally acting antagonism tecamylamine which alone was without effect in either model. Adopting a longitudinal design, the effects of chronic nicotine administration (3.16mg/kg/day for seven days, osmotic mini pumps), nicotine withdrawal and the residual sensitivity to nicotine following a sustained period of abstinence were then explored. Chronic nicotine administration enhanced disinhibition and impulsive choice, an effect that was greatest at the initial stages of treatment, suggesting that drug tolerance may have developed. Nicotine withdrawal had differential effects on impulsive choice and disinihibition. In the delay discounting task both initial and long-term withdrawal was associated with enhanced sensitivity to delayed reward. This effect, however, was restricted to low "trait" impulsive animals. Conversely, initial withdrawal induced a short-lived rebound increase in inhibitory control, following which a gradual decreasein inhibitory control was observed that reached significance during the second week of withdrawal. Evidence that the effects of nicotine on impulsivity were temporary was shown, with behaviour returning to base line levels three weeks following termination of treatment. Finally, acute nicotine challenges (0.125,0.25,0.5mg/kg, s. c. ) demonstrated that chronic nicotine exposurer endered animals hypersensitive to the effects of nicotine on disinhibition. Overall the present experimental investigations provide evidence to suggest that impulsivity may be a key componenant both the initial and end stages of addiction. Behavioural and pharmacological treatments that target impulsivity may prove to be effective future treatments for the disorder.
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6

Torres, Oscar Valentin. "Examination of the rewarding effects of nicotine during the adolescent period of development." To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2007. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.

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7

Cunningham, L. Joseph. "A stop smoking guide for the self-help quitting process." Virtual Press, 1994. http://liblink.bsu.edu/uhtbin/catkey/917044.

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The vast majority of smokers who manage to quit do so without the assistance of a facilitated cessation program. Since the majority of focused anti-smoking efforts are directed at facilitated programs, there is an apparent gap in service of the population at risk. Also, the sharp decline in smoking prevalence indicates a changing demographic dynamic. It is probable that those persons still smoking comprise a different population type than did smokers of a decade ago. A reexamination of major strategies for self-quitting is strongly indicated.The purpose of this thesis was to apply what was known about addictive behavior to a self-guided quitting process. Major variables guiding this effort were learning theory, theory of self-change, empirically demonstrated methods of cessation, and psychosocial effects on lifestyle change.The knowledge gained during the process was incorporated into a menu approach that emphasized personal responsibility for the quitting process and allows for choices that serve to tailor the program to the individual's needs. The end result was a quitters' guide, desktop published and prepared in a small quantity for pilot purposes. This guide was evaluated by persons with particular expertise in addictive behavior, especially smoking cessation. An ammended product was then presented to smokers and/or former smokers for further feedback. A journal of the process that detailed both difficulties and successes was also included.
Fisher Institute for Wellness
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8

Stennett, Bethany Ann. "Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats." UNF Digital Commons, 2013. http://digitalcommons.unf.edu/etd/465.

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The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process for both nicotine and alcohol. Considering the behavioral effects of NT69L in attenuating nicotine self-administration in rats and alcohol consumption in mice, the present study was designed to assess the effects of NT69L as a new drug. NT69L was used in the treatment of nicotine addiction in an animal model of alcoholics and in attempts to attenuate withdrawal signs associated with nicotine and alcohol dependence. Wistar rats pre-exposed to alcohol vapor or air were allowed to self-infuse nicotine (0.03mg/kg/infusion) or saline. When the rats reached a stable level of responding, the effect of pretreatment with NT69L (1mg/kg i.p.) on the reinforcing effect of nicotine was determined. Animals self-infused nicotine at a significantly (p < .05) higher rate compared to saline in both air and alcohol vapor exposed groups. Acute pretreatment with a single injection of NT69L significantly (p < .05) reduced nicotine self-infusion in both the alcohol vapor and the air exposed groups for 5 days post-injection. Additionally, NT69L attenuated the alcohol- and nicotine-induced withdrawal signs associated with the discontinuation of alcohol and nicotine administration. Neurotensin agonist, NT69L, may represent a potential novel therapy to treat the co-addiction of alcohol and nicotine.
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9

Thompson, Lauren. "Intracellular Signaling Contributions to Behaviors Relevant to Nicotine Addiction." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/253.

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Nicotine is the primary addictive substance in tobacco, and most smokers who quit will relapse within a year. Evidence shows that cigarette craving increases over time, termed “incubation.” The purpose of these studies was to see if protracted abstinence from chronic nicotine increases rat self-administration, an animal model with good face validity for human tobacco use, and if nicotine self-administration during daily exposure/after 8+ days of abstinence is regulated by extracellular signal-regulated kinase (ERK) signaling in the nucleus accumbens (NAc) shell or anterior cingulate cortex (PFC). ERK kinase inhibitor U0126 was infused in the NAc shell or PFC of Long Evans rats immediately prior to daily self-administration sessions and following 8+ days of abstinence. U0126 in the PFC decreased responding for nicotine during daily sessions. Following 8+ days of abstinence, animals showed a robust increase in responding for nicotine, blocked by U0126 in the NAc shell, but not the PFC. Western blots revealed that nicotine treatment decreased levels of a substrate of ERK, ribosomal s6 kinase (RSK), in the NAc shell and increased it in the PFC, which occurred independent of abstinence period. In contrast, levels of RSK were increased in the NAc shell following a nicotine challenge during the abstinence period. In summary, our data show that the ERK signaling pathway plays a vital role in nicotine addiction during daily nicotine exposure and following periods of abstinence.
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De, Preter C. C., Liza J. Hernandez, Seth L. Kirby, R. B. Campbell, E. Beaumont, C. A. Bradley, Matthew I. Palmatier, and Russell W. Brown. "Adolescent Methylphenidate Exposure Alters Nicotine Self-Administration and the Accumbal Firing Response to Nicotine." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/971.

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This study was designed to analyze the effects of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine self-administration, the motivation to obtain nicotine, and accumbal neuronal firing rate in female adolescent rats. MPH is the most commonly prescribed medication for Attention Deficit-Hyperactivity Disorder (ADHD) which is diagnosed in 3-5% of adolescents in the United States. However, this disorder is often misdiagnosed, and MPH is often prescribed to individuals not diagnosed with ADHD. Adolescent female Sprague-dawley rats were ip administered 1 mg/kg MPH or saline using a “school day” regimen of five days on, two days off, beginning on postnatal day (P)28 and this regimen was maintained throughout testing. A 1 mg/kg dose of MPH has been shown to result in brain plasma levels equivalent to clinical dosing in humans. Indwelling catheters were implanted in the jugular vein at P35, and one week later on P42, animals began nicotine self-administration. MPH (1 mg/kg) was administered each day approximately 6 h before each self-administration session began, which allows for nearly full plasma clearance of MPH (half-life = 1 h) before self-administration commenced. Rats were reduced to 85% of their free-feeding body weight and sipper tubes were made available to the rats in this paradigm, and responses to licking the tube produced an infusion of nicotine solution (15μg/kg) over a range of fixed ratio (FR) reinforcement schedules followed by a progressive ratio (PR) schedule, a measure of motivation. The schedule of reinforcement during 60 min sessions was increased from an FR5 to FR15 over approximately a three-week period. Results revealed that MPH pre-exposed rats self-administered significantly higher amounts of nicotine as compared to animals treated with saline throughout the FR5 and FR10 schedules. Further, MPH enhanced the motivation to self-administer nicotine on the PR schedule compared to controls, demonstrating an enhanced motivation to obtain nicotine produced by MPH. Finally, animals that had been pre-exposed to MPH and self-administered nicotine demonstrated a lower rate of basal accumbal firing as compared to controls, but a burst firing in response to nicotine that was higher than rats pre-exposed to saline. In conclusion, MPH altered the behavioral and neural response to nicotine in the nucleus accumbens.
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11

Bracken, Amy L. "Effects of nicotine exposure in adolescent rats on acquistion of alcohol drinking and response to nicotine in adulthood." Connect to resource online, 2009. http://hdl.handle.net/1805/1950.

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Thesis (Ph.D.)--Indiana University, 2009.
Title from screen (viewed on September 30, 2009). Department of Medical Neuroscience, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): William J. McBride, R. Andrew Chambers, James M. Murphy, Zachary A. Rodd. Includes vita. Includes bibliographical references (leaves 131-143).
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Hayward, Robert C. "The significance of withdrawal in a multidisciplinary profile of tobacco dependence." Thesis, University of Bristol, 2003. http://hdl.handle.net/1983/fecadd04-2154-439a-baa3-7ba3fa983ecc.

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13

Yerardi, Ruth Schroeder. "Biobehavioral nicotine dependence in persons with schizophrenia." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1172512647.

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14

Kummer, Sami 1985. "Involvement of pre-proenkephalin and sigma-1 receptors in nicotine addiction." Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/669683.

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El tabaquismo es la principal causa de muerte evitable en todo el mundo, responsable de más de 7 millones de muertes al año. La nicotina es el principal componente psicoactivo del tabaco y la responsable de sus propiedades adictivas. Aunque dejar de fumar produce importantes beneficios para la salud, alrededor del 80% de los ex fumadores recaen en el primer mes. La nicotina actúa sobre los receptores de acetilcolina nicotínicos, sin embargo, la adicción a la nicotina es una enfermedad cerebral compleja que implica la participación de varios sistemas de neurotransmisores. En un primer enfoque, combinamos sofisticados modelos de comportamiento operante con herramientas genéticas y quimiogenéticas mediadas por virus para demostrar que la señalización de opioides y la señalización glutamatérgica corticostriatal contribuyen de manera crítica a las propiedades de refuerzo de la nicotina. Además, revelamos que la autoadministración de nicotina desencadena la plasticidad estructural en la zona central y la corteza del núcleo accumbens (NAc). Curiosamente, la plasticidad estructural fue impulsada exclusivamente por la autoadministración contingente de nicotina, pero no por la administración no contingente, concluyendo que el comportamiento dirigido a objetivos y el condicionamiento son necesarios para activar los mecanismos que subyacen a la plasticidad estructural. En un segundo enfoque, demostramos por primera vez la implicación del receptor sigma-1 (Sig-1R), un nuevo tipo de receptor que se cree que carece de su propia maquinaria de señalización específica, en la recaída la búsqueda de nicotina. El bloqueo agudo de Sig-1Rs disminuyó significativamente el restablecimiento de la búsqueda de nicotina inducida por estimulos asociados al inhibir las adaptaciones neurobiológicas en la corteza prefrontal medial y el NAc, incluidos los receptores Sig-1R, glutamatérgicos, colinérgicos y opioides. En conjunto, nuestro estudio proporciona nuevos conocimientos sobre la participación de la señalización opioide, glutamatérgica y Sig-1R en la adicción a la nicotina que pueden ayudar a desarrollar nuevas estrategias terapéuticas para tratar la adicción a la nicotina.
Tobacco smoking is the leading cause of preventable death worldwide, responsible for more than 7 million deaths per year. Nicotine is the main psychoactive component of tobacco and responsible for its addictive properties. Although smoking cessation produces significant health benefits, around 80% of former smokers relapse within the first month. Nicotine acts on nicotinic acetylcholine receptors, however, nicotine addiction is a complex brain disease that involves the participation of several neurotransmitter systems. In a first approach, we combined sophisticated operant behavioral models with genetic and virus-mediated chemogenetic tools to demonstrate that opioid signaling and corticostriatal glutamatergic signaling critically contribute to the reinforcing properties of nicotine. We further revealed that nicotine self-administration triggers structural plasticity in the nucleus accumbens (NAc) core and shell. Interestingly, structural plasticity was singularly driven by contingent nicotine self-administration, but not non-contingent nicotine administration, concluding that goal-directed behavior and conditioning are necessary to trigger the mechanisms that underly structural plasticity. In a second approach, we demonstrated for the first time the implication of the sigma-1 receptor (Sig-1R), a novel receptor type that is thought to lack its own specific signaling machinery, in the relapse to nicotine-seeking. Acute blockade of Sig-1Rs significantly decreased cue-induced reinstatement of nicotine-seeking by inhibiting neurobiological adaptations in the medial prefrontal cortex and NAc, including Sig-1Rs, glutamatergic, cholinergic and opioid receptors. Together, our study provided new insights about the involvement of opioid, glutamatergic and Sig-1R signaling in nicotine addiction that can help to develop new therapeutic strategies to treat nicotine addiction.
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Zhao, Zongmin. "Factors that Affect the Immunogenicity of Lipid-PLGA Nanoparticle-Based Nanovaccines against Nicotine Addiction." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/88033.

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Tobacco smoking has consistently been the leading cause of preventable diseases and premature deaths. Currently, pharmacological interventions have only shown limited smoking cessation efficacy and sometimes are associated with severe side effects. As an alternative, nicotine vaccines have emerged as a promising strategy to combating nicotine addiction. However, conventional conjugate nicotine vaccines have shown limited ability to induce a sufficiently strong immune response due to their intrinsic shortfalls. In this study, a lipid-poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based next-generation nicotine vaccine has been developed to overcome the drawbacks of conjugate nicotine vaccines. Also, the influence of multiple factors, including nanoparticle size, hapten density, hapten localization, carrier protein, and molecular adjuvants, on its immunogenicity has been investigated. Results indicated that all these studied factors significantly affected the immunological efficacy of the nicotine nanovaccine. First, 100 nm nanovaccine was found to elicit a significantly higher anti-nicotine antibody titer than the 500 nm nanovaccine. Secondly, the high-density nanovaccine exhibited a better immunological efficacy than the low- and medium-density counterparts. Thirdly, the nanovaccine with hapten localized on both carrier protein and nanoparticle surface induced a significantly higher anti-nicotine antibody titer and had a considerably better ability to block nicotine from entering the brain of mice than the nanovaccines with hapten localized only on carrier protein or nanoparticle surface. Fourthly, the nanovaccines carrying cross reactive materials 197 (CRM197) or tetanus toxoid (TT) showed a better immunological efficacy than the nanovaccines using keyhole limpet hemocyanin (KLH) or KLH subunit as carrier proteins. Finally, the co-delivery of monophosphoryl lipid A (MPLA) and Resiquimod (R848) achieved a considerably higher antibody titer and brain nicotine reduction than only using MPLA or R848 alone as adjuvants. Collectively, the findings from this study may lead to a better understanding of the impact of multiple factors on the immunological efficacy of the hybrid nanoparticle-based nicotine nanovaccine. The findings may also provide significant guidance for the development of other drug abuse and nanoparticle-based vaccines. In addition, the optimized lipid-PLGA hybrid nanoparticle-based nicotine nanovaccine obtained by modulating the studied factors can be a promising candidate as the next-generation nicotine vaccine for treating nicotine addiction.
PHD
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Watkins, Shelly S. "Opponent process and nicotine addiction : perpetuation of dependence through negative reinforcement processes /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC IP addresses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9963666.

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Brown, Russell W., Amanda M. Maple, Marla K. Perna, A. Brianna Sheppard, Zackary A. Cope, and Richard M. Kostrzewa. "Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model." Digital Commons @ East Tennessee State University, 2012. https://doi.org/10.1159/000338830.

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Henderson, Brandon J. "Discovery and Characterization of Selective Negative Allosteric Modulators of Human α4β2 Neuronal Nicotinic Receptors." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1307647472.

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19

Amantea, Diana. "Study of GABA←B receptor mechanisms on the mesocorticolimbic system of nicotine dependent rats." Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273728.

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20

Kleykamp, Betha A. "The Effects of Transdermal Nicotine on Tobacco/Nicotine Withdrawal and Concurrently Administered Cigarettes in Women and Men." VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd/1218.

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Transdermal nicotine (TN) is a smoking cessation pharmacotherapy thought to work by suppressing tobacco/nicotine withdrawal and reducing the effect of a concurrently smoked tobacco cigarette. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of gender differences in response to transdermal nicotine in 54 women and 70 men. Participants completed four within-subject, double-blind, randomized sessions corresponding to 0, 7, 14, and 21 mg TN and 4-hrs after TN application smoked an own-brand cigarette. Prior to session onset participants completed ≥ 8 hours of verified tobacco cigarette abstinence (i.e., expired air carbon monoxide levels ≤ 10 ppm). Subjective and physiological measures were administered throughout each session, and cognitive performance and smoking behavior were assessed at time points related to the smoking opportunity.Results revealed that there were few significant effects involving the gender factor across withdrawal suppression and concurrent smoking outcomes (13 significant gender-related effects out of 338 possible; 3.9%). Women were more sensitive to some of the direct effects of nicotine in the 21 mg TN condition (e.g., increased ratings of "Nauseous"). However, for women and men TN suppressed some of the signs and symptoms of withdrawal and attenuated smoking-related increases in heart rate and subjective effects that might be indicative of the positive reinforcing properties of smoking (e.g., "Was the cigarette satisfying?"). In addition, for women and men, TN did not attenuate properties of smoking that might be negatively reinforcing (e.g., smoking- induced reductions in withdrawal symptoms). Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that NRT might be more efficacious if combined with other interventions that supplement the withdrawal suppressing effects of TN and reduce the negative reinforcing qualities of smoking.
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21

Bisch, Ochoa Laura. "Rx for change nurses' responses to a smoking cessation intervention /." Diss., St. Louis, Mo. : University of Missouri--St. Louis, 2009. http://etd.umsl.edu/r4221.

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22

Peterson, Daniel, A. Brianna Sheppard, Matthew I. Palmatier, and Russell W. Brown. "Adolescent Methylphenidate Exposure Increases the Reinforcement Enhancing Effects of Nicotine." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/963.

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Methylphenidate (MPH) is widely prescribed during childhood and adolescence for treatment of attention deficit and hyperactivity disorder. MPH is also one of the most commonly abused prescription drugs. However, the effects of MPH exposure and MPH abuse on incentive motivation are not well known. Moreover, MPH abuse during adolescence could increase sensitivity to the incentive motivational effects of other abused drugs such as nicotine in adulthood. Thus, the goals of this experiment were to investigate the effects of MPH exposure on the motivation to obtain sucrose during adolescence and to examine whether adolescent methylphenidate exposure altered the incentive motivational effects of nicotine (NIC) in adulthood. Incentive motivation was measured using an operant conditioning paradigm with sucrose available under a progressive ratio schedule of reinforcement (PR). Adolescent female rats were used because our previous studies have shown stronger sensitization to the locomotor stimulant effects of MPH. Rats arrived at post-natal day 21 (P21) and were shaped to respond for sucrose (20% w/v) on the PR schedule beginning on P24. After stable operant responding was established, rats were randomly assigned to receive either MPH (n=7) or SAL (n=6) injections (intraperitoneal) 30 min prior to test sessions, with the constraint that sucrose rewards earned did not differ between groups. Injection tests began on P36 and were carried out on alternating days for 10 total tests (P36-54). Although there was a trend for increased motivation for sucrose in the MPH group, it did not reach statistical significance. No further testing occurred until the rats reached adulthood (P55-P78). Over the next 5 days (P79-P84), all rats were pretreated with subcutaneous NIC injections (0.4 mg/kg base) 15 min before testing sessions. Following this initial ‘sensitization’ period, rats were tested with different NIC doses (0-1 mg/kg base) from P85-P92. During the sensitization period, NIC increased responding equally in both groups. However, during the dose-response testing, rats in the MPH group were more sensitive to the incentive motivational effects of NIC - the median effective dose was significantly lower for rats exposed to MPH in adolescence. The findings suggest that MPH may have limited reinforcement enhancing effects in adolescents. However, exposure to MPH during adolescents may increase the incentive motivational effects of NIC in adulthood.
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23

Peterson, Daniel J., Jim Wherry, Elizabeth D. Cummins, Don Hoover, and Russell W. Brown. "The Role of the Α7 and Α4β2 Nicotinic Receptors in Nicotine Sensitization and Neural Plasticity of Adolescent Rats Neonatally Treated with Quinpirole: Effects on Mtor and Nicotinic Receptor Density." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/2769.

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Aims: (1) Analyze the roles of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine sensitization in adolescent male and female rats neonatally treated with quinpirole as well as their effects on brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) 1 h and 24 h post drug treatment. (2) Analyze the effects of behavioral sensitization to nicotine on α7 and α4β2 nAChR density in the nucleus accumbens and dorsal striatum. Methods: Animals were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1-21. Beginning on P33, animals were ip injected with nicotine (0.5 mg/kg free base) or saline and tested every second day from P33-49. Approximately 30 min before injection, animals were ip injected with either the α7 nicotinic receptor (nAChR) antagonist methllycacontine (MLA; 2 or 4 mg/kg) or the α4β2 nAChR antagonist dihyro-β-erythrodine (DhβE; 1 or 3 mg/kg). Brain tissue was taken either 1 h or 24 h after the last day of testing. In a second experiment, animals were identically treated and brain tissue analyzed for nAChR density using the autoradiographic technique. Results: Neonatal quinpirole enhanced nicotine sensitization and the 3 mg/kg dose DhβE effectively blocked nicotine sensitization on Day 9 but enhanced the hypoactive response to nicotine on Day 1. MLA appears more important in the acute response to nicotine. Neonatal quinpirole sensitized the accumbal BDNF response to nicotine, but resulted in a decrease of accumbal mTOR. The nAChR density data will be presented. Conclusions: The α4β2 receptor played a critical role in the development of adolescent nicotine sensitization, and both nAChRs appear to be important in accumbal BDNF and in the mTOR response, demonstrating their important role in synaptic strength.
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24

Crawford, Caroline. "The effects of smoking cessation on changes in dietary intake." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0002/MQ44152.pdf.

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25

Murray, Heather W. Herbert James D. "The impact of brief acceptance-based versus control-based interventions on distress tolerance in early lapsing nicotine dependent individuals /." Philadelphia, Pa. : Drexel University, 2007. http://hdl.handle.net/1860/1793.

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26

Daniels, Karin Elizabeth. "Hookah pipe use : comparing male and female university students' knowledge, risk perceptions and behaviours." University of the Western Cape, 2012. http://hdl.handle.net/11394/5109.

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Magister Artium - MA
Hookah pipe use is widely viewed as a safe alternative to cigarette smoking rather than a potential health-risk. In fact, for young people hookah pipe use may represent an initial stage of later addiction and the transition to cigarette smoking. Furthermore, studies conducted abroad, suggest that the use of the hookah pipe firstly started as a cultural phenomenon, and secondly, as with cigarette smoking, the hookah pipe has become a social phenomenon. Despite these challenges, studies provide sufficient evidence that hookah pipe use is a potential health risk. The primary aim of the study was to compare male and female university students’ knowledge, risk perceptions and behaviours concerning hookah pipe smoking. A quantitative methodological approach, with a cross-sectional design, was used to conduct the research study. A final self-selected sample of 389 participants voluntarily participated in this study. The final sample included 64% females and 36% males with a mean age of 22.2 years; with the mean age for first-time hookah pipe smoking was 15.7 years. The instrument used was a self-administered questionnaire constructed from The College Health Behavior Survey (2010-2011) which was developed at the University of Missouri-Columbia. Descriptive quantitative results were conducted using Statistical Package for Social Sciences (SPSS version 20) and presented. The results suggest 70% of hookah pipe users daily smoke the hookah pipe with more than 20% smoking on campus. This was similar for males and females. Users perceived the hookah pipe to be less harmful and less addictive than cigarette smoking. Furthermore, smoking the hookah pipe is considered socially acceptable and is also smoked in the family home. Implications for policy are stated.
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27

Valverde, Sébastien. "Diversity of dopaminergic responses to drugs : a novel organizing principle of concurrent excitation and inhibition." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066679.

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Les neurones dopaminergiques (DA) de l'aire tegmentale ventrale (VTA) sont au cœur du système de la récompense. Ils sont impliqués dans la transmission de messages liés au contrôle motivationnel et à l'apprentissage par renforcement, permettant de mettre en place des comportements adaptés à l'environnement, mais ont aussi un rôle important dans la mise en place des addictions. Les neurones DA de la VTA projettent majoritairement vers le Noyau Accumbens (NAc) et vers le Cortex Préfrontal (PFC). Ces neurones sont la cible des drogues d'abus qui ont toutes en commun une capacité à augmenter les niveaux de dopamine dans les structures cibles. En effet, les drogues agissent au niveau des neurones DA, ce qui provoque un détournement du système de récompense et mène à l'addiction. La nicotine module le système DAergique à travers ses actions sur les récepteurs nicotiniques à l'acétylcholine (nAChRs), qui sont fortement exprimés dans la VTA. Ainsi la nicotine provoque l'augmentation de la concentration de DA dans les zones de projection, ce qui sous-tendrait le développement de comportements maladaptés liés à une prise de drogue excessive. Néanmoins cette augmentation apparente du relargage de DA dissimule la complexité de la réponse du système DAergique à la nicotine. En effet, les neurones DA forment une population hétérogène qui ne répond pas uniformément ni aux évènements ni aux drogues. Ainsi mon travail s'est focalisé sur la caractérisation de la réponse hétérogène des neurones DA de la VTA à la nicotine. Contrairement à ce qui est communément accepté dans la littérature, la nicotine n'induit pas une augmentation généralisée de l'activité des neurones DA. Ainsi, j'ai pu analyser une sous-population DAergique qui est inhibée par la nicotine. Ces réponses à la nicotine simultanées et opposées sont anatomiquement dépendante, la population inhibée étant localisée de manière plus médiale dans la VTA que la population activée. Nous montrons que cette inhibition requiert l'activation de récepteurs DA inhibiteurs, et pourrait donc être médiée par un relargage de DA intra-VTA. Malgré le fait que nous observons aussi une ségrégation anatomique des réponses DAergiques à des évènements aversifs, ces réponses ne sont pas corrélées à celles induites par la nicotine et sont organisées de manière dorso-ventrale plutôt que médio-latérale, ce qui suggère que le message DAergique transmis en réponse à la nicotine n'est pas le même que celui transmis par l'aversion. De plus, nous avons trouvé que les réponses excitatrices et inhibitrices sont aussi induites pas d'autres drogues d'abus comme l'alcool et les benzodiazépines. Cela suggère que ces réponses peuvent être étendues à d'autres stimuli, mais aussi qu'il existe un principe d'organisation de la VTA qui est anatomiquement défini, par lequel la VTA latérale interagit avec la VTA médiale à travers un effet de réseau local
Midbrain dopamine (DA) neurons of the ventral tegmental area (VTA) are at the center of the brain's reward system. They are involved in many different brain processes such as motivation, associative learning and reinforcement, and are critically involved in the pathophysiology of addiction. VTA DA neurons mostly project to the Nucleus Accumbens (NAc) and the Prefrontal Cortex (PFC) where they send signals related to motivational control. The common feature of drugs of abuse relates to their ability to increase DA levels in these regions. Indeed, drugs target VTA DA neurons, derailing the system from its natural reward-processing functions, which is thought to be the underlying neurophysiological mechanism leading to addiction. Nicotine is known to modulate the DAergic system through its actions on nicotinic acetylcholine receptors (nAChRs), which are highly expressed in the VTA. This results in an increase of DA concentrations in the areas of projection, which leads to the maladaptive behavior of nicotine addiction. However this apparent increase of DA release conceals the complexity of the system's response to nicotine. Indeed, DA neurons consist of a very heterogenous population, and don't respond uniformly to events or to addictive drugs. Thus my work has focused on the characterization of VTA DA neuron's heterogenous responses to nicotine. In contrast to the commonly acknowledged excitatory effect of nicotine on DA neurons, I've analyzed a subpopulation of DA neurons which are inhibited by nicotine. These concurrent but opposite responses to nicotine occur in an anatomically-dependent manner, with the inhibited population being localized more medially within the VTA compared to the activated population. We show that this inhibition requires the activation of inhibitory dopamine receptors, and could thus be mediated by an intra-VTA DA release. Although we also observe anatomically segregated excitatory and inhibitory responses to painful stimuli, these responses do not correlate to the ones induced by nicotine and are organized in a dorso-ventral fashion rather than a medio-lateral one, suggesting that the DAergic message conveyed by nicotine does not match the one conveyed by aversion. Moreover, we found that concurrent excitatory and inhibitory responses are also induced by other drugs of abuse such as ethanol and benzodiazepines. This suggests that these responses can be extended to other stimuli, but also that there exists an anatomically defined organizing principle of the VTA, in which the lateral VTA interacts with the medial VTA via a local network effect
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28

Maartens, Pieter Johann. "Investigating the effects of nicotine on the male reproductive system." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/85759.

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Thesis (MScMedSc)-- Stellenbosch University, 2013.
ENGLISH ABSTRACT: Much has been documented about the detrimental effects of adverse lifestyle factor exposure on the body. Exposure to factors, such as cigarette smoke, have proved to not only be a burden on global health and economy, but have also led to growing concerns about effects on systemic functions such as reproduction. The aim of the present study was to determine the effects of in utero and in vitro nicotine exposure on spermatozoal function and the antioxidant enzyme activity and lipid peroxidation (LPO) status of the male reproductive system. A better understanding of this process is necessary to combat the respective burdens of smoking and male infertility and for the prospective development of treatment strategies. Two experimental models were employed: Wistar rats were exposed to nicotine in utero while human and rat spermatozoa were exposed to nicotine in vitro. In utero studies were achieved by selecting healthy pregnant rats and treating them with 1 mg/kg-bodyweight/day nicotine or 1 ml/kg-bodyweight/day 0.85% physiologic saline throughout gestation and lactation. Male rat pups were selected and sacrificed at each of the following age groups (n=6): 42 days, 84 days and 168 days old. The pups were only exposed to the treatment/saline via placental uptake or lactation. Biochemical analyses of the tissue comprised of measurement of LPO and antioxidant enzyme activity. Results indicated a significant association of maternal nicotine exposure to decreased levels of primary antioxidant enzymes in rat testes. Of particular note was the observation that the treatment group, of which each of the respective antioxidant enzyme levels were significantly less than the control group, was the oldest (d168) rat group. In vitro studies were achieved by collecting sperm samples from healthy human donors (n=12), healthy rats (n=6) and obese rats (n=6). Samples were washed and exposed to different concentrations of high levels of nicotine (Control, 0.1mM, 1mM, 5mM, 10mM) in vitro. Semen parameters such as motility, viability and acrosome reaction were monitored at different time points (30min, 60min, 120min, 180min). Results revealed increasing in vitro nicotine concentrations were associated with decreased viability and acrosomal status of human spermatozoa and decreased progressive motility and viability of rat spermatozoa. Obesity was also associated with decreases in progressive motility and viability of rat spermatozoa. These results indicate that the acute in vitro exposure of spermatozoa to high levels of nicotine could adversely affect semen quality and may be an additive factor to the impediment of male fertility. In utero results reveal maternal nicotine exposure adversely affects male fertility in later life and seems to elicit more detrimental effects on the reproductive system than that of direct nicotine exposure to spermatozoa. Obesity also inhibits parameters of male fertility and these effects are exacerbated by nicotine exposure. The authors believe these adverse effects on the reproductive system to be related to an increased activation of leukocytes, excess production in reactive oxygen species (ROS) and consequent onset of oxidative stress (OS). Nevertheless this study agrees with other studies that nicotine exposure may be an additive factor to the impediment of male fertility.
AFRIKAANSE OPSOMMING: Daar is reeds baie bekend oor die moontlik newe effekte vir die liggaam wat met ‘n ongesonde lewenstyl gepaard gaan. Menslike blootstelling aan sulke faktore, soos sigaret rook, is wêreldwyd ‘n las vir gesondheid en ekonomie en het gelei tot geweldige kommer onder navorsers oor die moontlike komplikasies vir liggaamlike funksies soos voortplanting. Die doel van die betrokke projek was om die effekte van in utero en in vivo nikotien blootstelling op die antioksiderende ensiem aktiwiteit en lipied peroksidasie status van reproduktiewe weefsel en die funksionele parameters van spermatozoa te bepaal. ‘n Beter begrip van hierdie proses is noodsaaklik om die las van rook en vetsug teen te werk en vir die moontlike ontwikkeling van behandelingsstrategieë. Twee eksperimentele modelle is ontwerp: Wistar rotte is in utero blootgestel aan nikotien terwyl mens- en rot- spermatosoë ook in vitro aan nikotien blootgestel is. Vir die in utero studie is gesonde dragtige rotte gedurende swangerskap en laktasie met 1 mg/kgliggaamsgewig/ dag nikotien of 1 ml/kg-liggaamsgewig/dag 0.85% fisiologiese soutoplossing behandel. Manlike welpies is gekies en geoffer op elk van die volgende ouderdomme (n=6): 42 dae, 84 dae en 168 dae. Die welpies is slegs aan nikotien blootgestel deur plasentale opname en laktasie. Biochemiese analise van die testikulêre weefsel het ‘n beduidende assosiasie getoon tussen maternale nikotien blootstelling en verminderde vlakke van die primêre antioksiderende ensieme. Die 168 dag oue groep het ‘n merkbare vermindering getoon tussen kontrole en nikotien weefsel vir elk van die antioksiderende ensieme. Vir die in vitro studie is sperm monsters verkry vanaf gesonde mans (n=12), gesonde rotte (n=6) en vet rotte (n=6). Monsters is gewas en in vitro blootgestel aan verskeie hoë vlakke van nikotien (kontrole, 0.1mM, 1mM, 5mM, 10mM). Seminale parameters soos motiliteit, lewensvatbaarheid en akrosoom status is by verskei tydpunte gemeet (30min, 60min, 120min, 180min). Dit blyk dat verhoging in in vitro nikotien konsentrasies verband hou met verlaagde lewensvatbaarheid en akrosoom status van menslike spermatosoë en verlaagde progressiewe motilteit en lewensvatbaarheid van rot spermatosoë. Vetsug is ook geassosieer met verlagings in progressiewe beweeglikheid en lewensvatbaarheid van rot spermatosoë. In utero resultate openbaar dat maternale nikotien blootstelling manlike vrugbaarheid nadelig beïnvloed in latere lewe en blyk dat dit meer van ‘n nadelige uitwerking op die voortplantingstelsel het as dié van direkte nikotien blootstelling aan spermatosoë. In vitro blootstelling van spermatosoë aan hoë vlakke van nikotien, het wel ook semen kwaliteit nadelig beïnvloed. Vetsug inhibeer ook manlike vrugbaarheids parameters en hierdie effek word vererger deur nikotien blootstelling. Die outeure glo dat hierdie nadelige uitwerking op die voortplantingstelsel verband hou met 'n verhoogde aktivering van leukosiete, oortollige produksie van reaktiewe suurstof spesies en die gevolglike aanvang van oksidatiewe stres bevorder. Hierdie studie stem wel ooreen met ander studies wat nikotien blootstelling bestempel as ‘n bydraende faktor tot die struikelblok van manlike onvrugbaarheid.
Harry Crossley Foundation (South Africa)
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29

David, Sean P. "Studies of genetic influences on nicotine dependence utilising functional neuroimaging." Thesis, University of Oxford, 2005. http://ora.ox.ac.uk/objects/uuid:37d9fe42-d1a4-4bb4-82d0-88c399be1f86.

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A major contributor to relapse following smoking cessation is nicotine craving triggered by environmental cues, such as the sight of a lighted cigarette. Therefore, three integrated functional neuroimaging studies were conducted to examine the biological mechanisms underling cue-elicited craving for cigarettes. (1) First, I examined the effect of smoking-related pictorial cues on neural activation hi brain regions of interest (ROI) associated with reward signalling using functional magnetic resonance imaging (fMRI). Voxel-wise analysis demonstrated that smokers, but not nonsmokers, demonstrated significant activation associated with smoking-related pictorial cues in the anterior cingulate cortex, orbitofrontal cortex, and ventral striatum. Upon ROI analysis of the ventral striatum including the nucleus accumbens (VS/NAc), smokers exhibited significantly greater VS/NAc activation than non-smokers. (2) Next, I examined whether pre-specifled serotonergic polymorphisms would affect binding potential (BP) to a serotonin (5-HT) receptor implicated in the behavioural sensitisation process to nicotine (5-HTiA receptor). Healthy volunteers who had undergone positron emission tomography (PET) with a 5-HTiA-specific ligand [ U C]WAY-100635 were genotyped for the 5-HT1 A -1018 G>C and 5-HT transporter (5-HTT) 5-HTT gene-linked polymorphic region (5-HTTLPR) polymorphisms. Participants carrying the 5-HTTLPR S allele (SS or SL genotypes) demonstrated significantly lower global presynaptic and postsynaptic BP compared to subjects with LL genotypes. (3) Finally, I triangulated the two initial studies to examine whether pre-specified trait (5- HTTLPR genotype) and/or state (smoking vs. abstinence) variables would influence cueelicited activation of the VS/NAc. There was greater activation to smoking-related cues in the VS/NAc of smokers during the smoking condition than the abstinent condition and a significant correlation between tobacco craving and VS/NAc activation in the smoking condition. The 5-HTTLPR polymorphism was not associated with VS/NAc activation. Power calculations are presented as the basis for future examination of genetic hypotheses. These data have implications for the ultimate goal of enhancing the efficacy of smoking cessation pharmacotherapy.
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30

Scanlin, Matthew C. "The Effects of Stress-Related Rumination Versus Distraction on Nicotine Cravings and Latency to Smoke among Nicotine-Deprived Smokers." Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1572553054250324.

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31

Molas, Casacuberta Susanna 1985. "Nicotine addiction phenotypes in a BAC transgenic mouse model overexpressing the CHRNA5/A3/B4 genomic cluster." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/104155.

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The CHRNA5/A3/B4 genomic cluster encodes for the alpha5, alpha3 and beta4 subunits of the nicotinic acetylcholine receptors (nAChRs). Human genetic studies have revealed a significant association of variants in this genomic region with nicotine dependence. However, the mechanisms through which overexpression of these three subunits may influence smoking-related behaviours is not understood. To gain insight in the possible mechanisms, we used a BAC transgenic mouse model overexpressing this cluster containing the three genes together with their transcriptional regulatory elements. We found that overexpression of the cluster: i) increases sensitivity to the pharmacological effects of nicotine; ii) modifies particular cognitive domains associated to drug addiction and hippocampal neuronal complexity and synaptic plasticity; and iii) shifts the rewarding and aversive properties of nicotine and the manifestation of nicotine-withdrawal syndrome. Our study suggests that the genomic cluster CHRNA5/A3/B4 contributes to genetic vulnerability to nicotine addiction and promotes smoking-related behaviours possibly through hippocampal plasticity changes.
El cluster genòmic CHRNA5/A3/B4 codifica per les subunitats alfa5, alfa3 i beta4 dels receptors d’acetilcolina (nAChRs). Estudis de genètica humana han revelat que variants en aquesta regió genòmica estan significativament associats a la dependencia a nicotina. Malauradament, els mecanismes pels quals la sobreexpressió d’aquestes tres subunitats influencia comportaments relacionats amb el consum de tabac no són del tot coneguts. Per tal d’entendre els possibles mecanismes, hem utilitzat un model de ratolí transgènic que sobreexpressa aquest cluster amb els tres gens i les seus elements de regulació transcripcional. Hem trobat que la sobreexpressió del cluster: i) incrementa la sensibilitat als efectes farmacològics de la nicotina; ii) modifica determinats dominis cognitius associats a l’addicció a droges i la complexitat neuronal i plasticitat sinàpica de l’hipocamp; a més a més iii) canvia les propietats de recompensa i aversió de la nicotina i la manifestació del síndrome d’abstinència. El nostre estudi suggereix que el cluster genòmic CHRNA5/A3/B4 contribueix a la vulnerabilitat genètica a l’adicció a la nicotina i promou comportaments relacionats amb el consum de tabac possiblement a través de canvis de plasticitiat a l’hipocamp.
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32

Perna, Marla K., and Russell W. Brown. "Adolescent Nicotine Sensitization and Effects of Nicotine on Accumbal Dopamine Release in a Rodent Model of Increased Dopamine D2 Receptor Sensitivity." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/956.

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Our laboratory has reported neonatal quinpirole (D2/D3 agonist) treatment to rats increases dopamine D2 receptor sensitivity that persists throughout the animal's lifetime. This model appears to have clinical relevance to schizophrenia, and smoking is common in this population. Male and female Sprague-dawley rats were neonatally treated with quinpirole from postnatal (P) days 1–21. After habituation from P30 to 32, animals were administered saline or nicotine (0.3, 0.5, or 0.7mg/kg free base) every other day from P33 to 49 and locomotor activity was assessed. Generally, animals neonatally treated with quinpirole and administered nicotine during adolescence demonstrated increased behavioral activity and/or sensitization compared to animals neonatally given saline and sensitized to nicotine as well as controls. However, animals neonatally treated with quinpirole and given the 0.7mg/kg dose of nicotine demonstrated elevated activity throughout testing but did not show sensitization, and only mild sex differences were reported. Therefore, microdialysis was performed on male rats sensitized to the 0.5mg/kg dose of nicotine, and results revealed that neonatal quinpirole sensitized dopamine overflow in response to nicotine to 500% above animals neonatally given saline and sensitized to nicotine at peak levels. In addition, neonatal quinpirole increased the accumbal BDNF in response to nicotine compared to all other groups, and nicotine alone also produced significant increases in striatal and accumbal BDNF. This study reveals that neonatal quinpirole enhanced adolescent nicotine sensitization, accumbal dopamine overflow, and BDNF protein in response to nicotine, which may be related to changes in the brain's reward system.
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33

Porter, Ailsa. "Immediate early gene expression in the mesopontine tegmentum and midbrain after acute or chronic nicotine administration." Thesis, St Andrews, 2008. http://hdl.handle.net/10023/507.

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34

Kirby, Seth, Katherine C. Burgess, L. A. Beuttel, Daniel J. Peterson, C. A. Bradley, Meng-Yang Zhu, Matthew I. Palmatier, and Russell W. Brown. "Nucleus Accumbens BDNF Overexpression Alters the Behavioral Response to Nicotine." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/967.

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Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in synaptic differentiation, growth, and maintenance. Increases in BDNF have been shown in substance abuse and decreases in BDNF have been shown in response to stress and major depressive disorder (MDD). We analyzed the effects of BDNF upregulation via lentivirus on Pavlovian conditioned approach (PCA), behavioral sensitization, and nicotine self-administration in rats. Lentiviral-mediated expression cassettes, with dual promoters to drive the BDNF gene and the reporter gene were constructed according to the manufacturer’s instruction and surgically injected into the nucleus accumbens (Nac), the primary brain area that mediates drug reward and reinforcement. Rats were allowed to recover for three weeks before behavioral testing commenced. All rats were trained to associate the presentation of a lever and illumination of a stimulus light with delivery of 20% sucrose in a Pavlovian conditioned approach (PCA) task. Head entries into the receptacle where sucrose was delivered (goal tracking) and lever pressing (sign tracking) during the conditioned stimulus (CS) were measured to determine if BDNF over-expression (BDNF+) altered approach to the sign or goal location. Rats in the BDNF+ group made more goal directed behaviors during the CS than sham group. There were no differences in sign tracking and no differences in basal activity. This pattern suggests that BDNF over-expression may increase reward-related learning in a manner specific to goal tracking. Three days after completion of the PCA task, all animals were habituated to a locomotor arena followed by nicotine behavioral sensitization, and were administered nicotine (ip, 0.5 mg/kg free base) or saline every second day for seven days. Results revealed that the BDNF+ group demonstrated enhanced sensitivity to the hypoactive response to nicotine. At day 7, BDNF+ animals demonstrated enhanced behavioral sensitization to nicotine as compared to all other groups, and Sham NIC animals demonstrated sensitization compared to Sham SAL controls. Thus, it appears increasing NAc BDNF expression enhances the behavioral response to nicotine. Animals were then surgically implanted with a jugular catheter and commenced nicotine self-administration. Interestingly, BDNF+ rats demonstrated reduced nicotine self-administration and motivation to obtain nicotine. Global changes in BDNF expression could be a mediating variable in endophenotypes that are more or less susceptible to drug-taking and substance dependence.
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35

Brock, Alistair James. "Identifying novel genes associated with response to nicotine in a zebrafish model of drug dependence." Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8905.

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Tobacco addiction is a leading preventable cause of death worldwide and places a heavy social and financial burden on society. There exists a substantial genetic variability in smoking behavior, the mechanisms of which are largely unknown. Despite significant advances in sequencing power, progress in the identification of genetic variants affecting smoking behavior based on human genome wide association studies has been slow. Thus this thesis investigates the utility of zebrafish as a model species in which to search for genetic variants affecting nicotine seeking. The work is based on the premise that as zebrafish are vertebrate with conserved neurochemical pathways and circuitry with humans, and the pathways involved in drug mediated reward and addiction are evolutionarily ancient, homologues of genes affecting zebrafish nicotine-seeking behavior will likely affect human smoking behavior. Thus results in zebrafish can be used to direct human genetic studies. The first result chapter addresses the hypothesis that zebrafish show conserved reward responses to common drugs of abuse. A conditioned place preference assay is used to assess zebrafish reward responses to stimulants, opioids, benzodiazepines and alcohol. The results indicate that, with the exception of benzodiazepines, reward responses are conserved, supporting the use of this model in a screen for genetic variants affecting nicotine preference. The second and third results chapters describe the findings of a pilot screen of ENU-mutagenized zebrafish provided by the Sanger Institute, Cambridge. I demonstrate that nicotine preference is heritable in fish as in Abstract 5 humans and identify 3 mutant lines that show increased or decreased nicotine place preference. Genotyping indicated that one of the families showing increased nicotine preference carries a predicted loss of function mutation in the slit3 gene. The involvement of this gene in nicotine preference was confirmed in a separate line. Further characterization of this line using qPCR showed slit3 mutants to have altered developmental expression of key nicotinic and dopaminergic genes. Having identified the slit3 gene as a locus affecting nicotine seeking in fish, I then tested the hypothesis that results in fish could be used to predict loci that affect human smoking behavior. Cohorts of patients were genotyped for 20 SNPs within the slit3 locus. Results of this analysis identified 1 novel SNP in the slit3 gene associated with smoking behavior in a cohort of individuals that were heavy smokers. This result was validated in cohorts of low and normal smoking prevalence. These data demonstrate the utility of behavioral assays in zebrafish to identify genes affecting human behavior and pave the way for the use of zebrafish to inform human studies exploring the genetic basis of drug seeking and behavioral disease.
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36

Peterson, Daniel J., Courtney M. Bardo, Elizabeth D. Cummins, and Russell W. Brown. "The Role of the Alpha7 and Alpha4 Beta2 Nicotinic Receptors in Nicotine Sensitization and Neural Plasticity in Rats Neonatally Treated with Quinpirole." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/959.

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Aims: We have established that neonatal treatment with quinpirole, a dopamine D2/D3 agonist, results in increases of dopamine D2 receptor sensitivity throughout the animal’s lifetime and has a number of consistencies with schizophrenia. Aim 1: Analyze the roles of α7 and α4β2 nicotinic receptors in nicotine sensitization in adolescent male and female rats neonatally treated with quinpirole. Aim 2: The roles of the α7 and α4β2 nicotinic receptors were analyzed in their effects on Brain-Derived Neurotrophic Factor (BDNF) and mammalian target of rapamycin (mTOR) in rats neonatally treated with quinpirole and sensitized to nicotine. Methods: Animals were neonatally treated with quinpirole or saline from postnatal days (P)1-21. Beginning on P33, animals were ip injected with nicotine (0.5 mg/kg free base) or saline and tested every second day from P33-49. Approximately 15-30 min before the nicotine or saline injection, animals were ip injected with either the α7 nicotinic receptor (nAChR) antagonist methllycacontine (MLA; 2 or 4 mgkg) or the α4β2 nAChR antagonist dihyro-β (DhβE; 1 or 2.5 mg/kg) erythrodine. Brain tissue was taken 24 h after the last day of testing. Results: Neonatal quinpirole enhanced nicotine sensitization and DhβE blocked nicotine sensitization regardless of neonatal treatment and was more effective in blocking sensitization in males versus females. MLA failed to block nicotine sensitization. Howeer, MLA blocked the acute hypoactive response to nicotine in males, and the higher dose of MLA reduced sensitization in males. Neonatal quinpirole sensitized the accumbal BDNF response to nicotine, but neonatal quinpirole resulted in a decrease of mTOR in both brain areas. Conclusions: The α4β2 receptor plays a critical role in adolescent nicotine sensitization. Interstingly, the α7 nAChR appears to be important in the acute response to nicotine and is more important in nicotine sensitization in males. Both nAChRs appear to be important in accumbal BDNF and their roles will be analyzed in the mTOR response.
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37

Tannous, Salma. "Rôle des stimuli sensoriels et de la palatabilité dans la prise orale de nicotine chez la souris." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0398.

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Les produits du tabac sont hautement addictifs et leur abus est un problème majeur de santé publique. Chez les humains, cette addiction met en jeu une expérience consommatoire orale avec des composantes sensorielles gustatives et olfactives. De nos jours, le rôle de ces composantes est amplifié avec l’utilisation accrue des produits du tabac non-brûlé, mais aussi les cigarettes électroniques, où la nicotine est associée à des additifs incluant flaveurs et sucres. L’impact des additifs sur le comportement de consommation du tabac doit donc être évalué. Dans ce travail de recherche, notre intérêt se porte sur la nicotine orale et l’interaction bidirectionnelle avec les flaveurs associées. Nous questionnons notamment les propriétés de renforcement secondaire, les effets des arômes sur la palatabilité de la nicotine et son encodage affectif. Dans un premier chapitre, nous avons investigué les propriétés irritantes de la nicotine dans un modèle d’auto-administration orale de nicotine diluée dans de la saccharine chez des souris génétiquement modifiées (knockout) pour le thermorécepteur TRPV1 (Transient receptor potential vanilloid 1), impliqué dans l’échauffement lié au tabagisme et qui a la particularité d’être sensibilisé par la nicotine. Nous mettons en évidence que l’absence de ce récepteur promeut la consommation de nicotine par diminution de son aversion orale. Il n’a cependant pas un rôle spécifique dans les mécanismes de motivation et de rechute. Il a été montré que les stimuli sensoriels non-pharmacologiques deviennent plus salients quand ils sont associés à la nicotine. Ainsi, nous étudions dans un deuxième chapitre, le renforcement secondaire putatif des stimuli oraux par la nicotine. Nous mettons en évidence la nécessité d’association orale de la nicotine à des additifs masquant son goût amer, afin de permettre sa consommation volontaire et la modélisation des différents stades du processus addictif. Ce processus se montre sensible aux stimuli dans la consommation et la rechute, mais insensible aux challenges pharmacologiques malgré l’absorption de nicotine mesurée par la présence de cotinine plasmatique. Les solutions de nicotine à fortes concentrations révèlent des propriétés aversives et réduisent la consommation volontaire. Bien que nous ne montrions pas le renforcement des propriétés incitatives de la vanille par la nicotine, de façon surprenante nous montrons que l’arôme seul peut renforcer le comportement d’auto-administration. Enfin, du fait de l’importance des effets sensoriels oraux dans la consommation de nicotine, nous avons étudié ses propriétés de palatabilité. Les tests de réactivité gustative montrent bien l’aversion gustative pour la nicotine seule et l’amélioration de la palatabilité par l’ajout d’additif aromatique. Ce changement de la palatabilité ne s’est néanmoins pas traduit par des changements du codage neuronal mesuré par le marquage de la protéine c-Fos dans les structures contribuant à l’expression de la valence positive ou négative, notamment le noyau accumbens, le cortex insulaire gustatif, le noyau basolatéral de l’amygdale, l’habenula et la noyau paraventriculaire du thalamus. En revanche, la nicotine, aromatisée ou non, a augmenté l’activation neuronale dans toutes ces structures. L’ensemble de ces résultats met en lumière cette problématique d’association de la nicotine aux additifs pouvant moduler sa perception sensorielle et promouvoir par la suite sa consommation. L’attractivité des nouveaux produits du tabac et leur potentiel d’abus est une question authentique et un problème de santé publique dont l’étude et la régulation sont urgentes
Tobacco products are highly addictive and their abuse is a major public health problem. In humans, this addiction constitutes an oral consummatory experience involving sensory gustatory and olfactory components. Nowadays, the role of these components is further amplified with the increasing use of new “heat not burn” tobacco products, electronic nicotine delivery device (e-cigarettes especially), where nicotine is associated with additives including flavours and sugars. Thus, the impact of additives on the behaviour of nicotine consumption must be assessed. In this research work, we are interested in oral nicotine and the bidirectional interaction with the associated flavours. In particular, we question the secondary reinforcing properties, the effects of aromas on the palatability of nicotine and its affective coding. In a first chapter, we investigated the irritating properties of nicotine in a model of oral self-administration in mice genetically modified (knockout) for the thermoreceptor TRPV1 (Transient receptor potential vanilloid 1) because it is involved in harshness and it is sensitized by nicotine. We highlight that the absence of this receptor promotes nicotine consumption by reducing its oral aversion. It does not, however, have a specific role in motivation and relapse mechanisms. It has been shown that non-pharmacological sensory stimuli become more salient when associated with nicotine. Here, we study the putative secondary reinforcement of oral stimuli by nicotine. We highlight the need for oral nicotine to be combined with additives that mask its bitter taste, to allow its volitional consumption and to be able to model the different stages of the addictive process. This process is sensitive to stimuli for consumption and reinstatement, but is unaffected by pharmacological challenges despite nicotine absorption measured by the dosage of plasma cotinine. High concentrations of nicotine solutions reveal its aversive properties and reduce oral self-administration in mice. Although we do not show the reinforcement of the incentive properties of vanilla by nicotine, we surprisingly show that the aroma itself can reinforce self-administration behaviour. Finally, because of the importance of the oral sensory effects in nicotine consummatory behavior, we studied its palatability properties. Taste reactivity tests show the aversive taste of nicotine alone and the enhancement of its palatability by the addition of aromatic additive. However this change in palatability did not result in changes in the neuronal coding, measured by the labelling of c-Fos protein in brain structures contributing to the expression of the positive and negative valence, notably the nucleus accumbens, the gustatory insular cortex, the basolateral amygdala, the habenula and the paraventricular nucleus of the thalamus. On the other hand, nicotine, flavoured or not, increased neuronal activity in all these structures. Altogether, these results highlight the importance of nicotine association with flavour additives that can modulate its sensory perception and subsequently promote its consumption. The attractiveness of new tobacco products and their abuse potential is a public health problem that needs urgent study and regulation
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38

Richter, William Thompson. "Parameters of nicotine titration in addicted and non-addicted cigarette smokers." Thesis, Virginia Polytechnic Institute and State University, 1986. http://hdl.handle.net/10919/91144.

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Nicotine titration was studied in cigarette smokers not interested in cutting down or quitting smoking. Forty smokers were classified as high nicotine dependent (n=20) and low nicotine dependent (n=20) using a validated tolerance questionnaire. Subjects were randomized into baseline (n=10) or nicotine fade conditions (n=10) within their dependency group. Subjects in the baseline conditions smoked their preferred brand of cigarette throughout the experiment. Smokers in the fade conditions switched to a reduced nicotine brand in the latter half of the procedure. Multiple in vivo and in vitro measures of smoking rate and topography were collected over a four day period. Based on analyses of these data, it was concluded that no compensatory changes in smoking behavior occurred that were clearly attributable to nicotine titration. It was found that smokers classified as high nicotine dependent smoked more intensively that low dependent smokers. The implications of these findings given the design and experimental controls employed in this experiment are discussed, and directions for future research explored.
M.S.
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39

Schlitt, M. A., Daniel J. Peterson, Elizabeth D. Cummins, and Russell W. Brown. "The Effects of Environmental Enrichment on Adolescent Nicotine Sensitization in a Rodent Model of Schizophrenia." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/974.

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Our lab has shown that neonatal treatment with quinpirole, a dopamine D2/D3 agonist, to rats resulted in an increase in dopamine D2‐like receptor sensitivity that persists throughout the animal’s lifetime without a change in receptor number, consistent with schizophrenia. Approximately 80‐85% of schizophrenics smoke cigarettes, and there is no delineated mechanism for this observation. Our lab has also shown more robust sensitization and accumbal dopamine release in response to nicotine in adolescent rats neontally treated with quinpirole compared to controls. This study analyzed whether environmental enrichment, known to reduce sensitization to psychostimulants, may also reduce or block enhanced sensitization to nicotine in this model. Male and female rats were treated with either quinpirole (1 mg/kg) or saline from postnatal day (P)1‐21. After weaning at P21, animals were raised in either environmentally enriched or isolated housing throughout the experiment. Beginning on P33, animals were ip administered either nicotine (0.5 mg/kg free base) or saline 10 min before placement in a square locomotor arena and behavioral activity measured every second day from P33‐49. Results revealed that animals given neonatal quinpirole treatment and reared in an enriched environment demonstrated more robust sensitization to nicotine than all other groups. Animals given neonatal quinpirole or saline treatment followed by nicotine in adolescence and raised in isolated housing conditions were equivalent, but demonstrated more robust sensitization compared to enriched rats Page 13 of 35 neonatally treated with saline and administered nicotine in adolescence. Results here show that environmental enrichment enhanced nicotine sensitization in rats neonatally treated with quinpirole, which is in contrast to the blockade of sensitization to nicotine which has previously been shown in normal animals. Importantly, these results show that increases in D2 receptor sensitivity interacts with environmental enrichment differently than in normal animals and the manner in which the animal responds to nicotine, which may have implications towards smoking cessation in schizophrenia.
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40

Wilkinson, Derek Scott. "Examination of tolerance to the cognitive enhancing effect of nicotine on contextual conditioning." Diss., Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/162397.

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Psychology
Ph.D.
Nicotine addiction is a multifaceted disease that can be influenced by several factors. Emerging evidence indicates that the neural substrates of nicotine addiction overlap with the neural substrates of learning and memory. Nicotine modulates various types of learning and memory and the ability of nicotine to alter cognitive processes may contribute to its addictive liability. Acute nicotine enhances contextual conditioning in mice, tolerance develops to this effect with chronic administration, and withdrawal from chronic nicotine produces cognitive deficits. While tolerance and withdrawal deficits both occur following chronic administration, it is unknown if they share similar mechanisms. The series of experiments in Chapter 2 were designed to provide evidence that tolerance and withdrawal are dissociable. C57BL/6J mice were implanted with osmotic minipumps that delivered constant nicotine or saline for various durations and then were trained and tested in contextual conditioning either during chronic nicotine administration or 24 hours after pump removal. Chronic nicotine enhanced contextual conditioning in a dose- and time-dependent manner. Tolerance developed quickly to the enhancing effect of chronic nicotine. Furthermore, the duration of chronic nicotine treatment required to produce cognitive deficits upon cessation of treatment differed than that required to produce tolerance, which suggests that tolerance and withdrawal are mediated by separate mechanisms. Chapter 2 concludes by presenting a model that integrates nicotinic acetylcholine receptor desensitization and upregulation to explain the present findings. The model presented in Chapter 2 predicts that there will be enhanced sensitivity to acute nicotine during a period of nicotine withdrawal. Previous research indicates that prior exposure to nicotine enhances sensitivity to acute nicotine injections, but it is unclear if this enhanced sensitivity is due to prior nicotine exposure or enhanced sensitivity to nicotine during withdrawal. Therefore, the experiments in Chapter 3 were designed to determine if prior exposure to nicotine or nicotine withdrawal altered sensitivity to acute nicotine injections. This was accomplished by assessing the effects of acute nicotine on contextual conditioning immediately after cessation of chronic nicotine treatment and two weeks later, a time period not associated with withdrawal-related changes in cognitive function. Results of the study showed that acute nicotine enhanced contextual conditioning across a wide range of doses in both saline- and nicotine-withdrawn mice. However, a greater enhancement of contextual conditioning was observed in mice withdrawn from chronic nicotine treatment for 24 hours than all other withdrawal groups, suggesting enhanced sensitivity during withdrawal. The enhanced sensitivity to acute nicotine suggests altered nAChR function during withdrawal. In addition, the lowest dose of acute nicotine did not enhance contextual conditioning in groups that received chronic nicotine but did in other groups. The simultaneous observation of a hyper and hyposensitive nAChR system during withdrawal suggests that there may be a phasic response to chronic nicotine. Together, the results of the present study suggest that tolerance and withdrawal operate under separate mechanisms, and that there is overall enhanced sensitivity to nicotine during periods of nicotine withdrawal.
Temple University--Theses
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41

Bernard, Amy Lynn. "A descriptive analysis of selected smoking cessation programs." Virtual Press, 1991. http://liblink.bsu.edu/uhtbin/catkey/774763.

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The purpose of this research was to compare and contrast the components and characteristics of selected widely available smoking cessation programs.To reach this goal, an evaluation form was developed after an extensive review of the literature which addressed the structure, duration, techniques, issues which were discussed, success rates and availability of the programs. This form was tested for content validity by a jury of experts and was used to review each of thirteen selected smoking cessation programs. The reviews were conducted by the author using program materials received from the sponsoring organizations. Any questions which could not be answered with these materials were answered through a telephone interview with a representative of the sponsoring organization.Once the reviews were completed, the information was transferred to table form and to a database so that collective data could be generated. The following conclusions were drawn from the table and the data generated: the existing smoking cessation programs appear to have been developed utilizing suggestions offered in to use similar program techniques, and a great deal of variance exists in terms of success rates and cost.
Department of Physiology and Health Science
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42

Ursprung, W. W. Sanouri A. "Developing Three New Pathophysiologically Based Measures of Nicotine Dependence: A Dissertation." eScholarship@UMMS, 2014. http://escholarship.umassmed.edu/gsbs_diss/714.

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BACKGROUND: Of the 22 known measures of nicotine dependence (ND), none capture the overall disease severity of physical dependence alone. Instead, they capture constructs related to dependence, such as perceived risk, psychological addiction, smoker motivations, or smoking related behaviors, but none of the measures include only physical withdrawal symptoms to capture physical dependence on nicotine. AIM: To develop a range of nicotine dependence measures that capture physical dependence on nicotine. METHODS: The final measures were developed in a cross-sectional study conducted in three phases: 1) candidate item development through literature review and cognitive interviews, 2) developing and pre-testing the survey, and 3) survey administration and psychometric evaluation to validate three distinct measures. The final survey was conducted at four health clinics and three high schools. Psychometric tests used to select the final measure items included inter-item correlations, sensitivity analyses done by subgroup, item-total correlations, convergent validity tests, and confirmatory factor analysis. The final measures were evaluated using confirmatory factor analysis (CFA), internal reliability, total score distributions, and convergent validity correlations. Relative validity analyses were also conducted using a ratio of F-Statistics to compare the ability of each new measure to differentiate dependent smokers as compared previous measures. RESULTS: The final sample included 275 smokers ranging from 14 to 76 years old (mean=30.9, SD=16.2), who smoked an average of 11.5 cigarettes per day (range=0-50, SD=9.4). The sample was 86.5% white and 57.5% male. The three new measures developed included: 1) the 4-item Withdrawal-Induced Craving Scale (WICS) used to capture severity of craving, the most common physical withdrawal symptom; 2) the 12- item Nicotine Withdrawal Symptom Checklist (NWSC), which measures both overall disease severity and the severity of a comprehensive list of individual physical withdrawal symptoms including withdrawal-induced craving, anger, anxiety, depression, headache, insomnia, loss of focus, restlessness, and stress; and 3) the 6-item brief NWSC (NWSC-b), a short measure which only captures overall disease severity. All of the new measures exhibited a unidimensional factor structure loading highly on a single factor (thought to be physical dependence). They also correlated highly (over 0.6) and significantly (p<0.001) to a battery of convergent validity indices including four widely used nicotine dependence measures: Hooked on Nicotine Checklist (HONC), the Autonomy Over Tobacco Scale (AUTOS), the Fagerström Test for Nicotine Dependence (FTND), and self-rated addiction. CONCLUSION: The WICS, NWSC, and NWSC-b provide three distinct validated tools that can be used by researchers, clinicians, and educators to track the progression of physical dependence on nicotine across a range of smoking behaviors and histories.
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43

Peterson, Daniel J., Wesley Drew Gill, John M. Dose, Donald B. Hoover, James R. Pauly, Elizabeth D. Cummins, Katherine C. Burgess, and Russell W. Brown. "The Effects of Nicotine in the Neonatal Quinpirole Rodent Model of Psychosis: Neural Plasticity Mechanisms and Nicotinic Receptor Changes." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/942.

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Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking.
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44

Raymond, Barrett H. "The Nicotine Content of a Sample of E-cigarette Liquid Manufactured in the United States." BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/6726.

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Background: Use of electronic cigarettes (EC) has dramatically increased in the United States since 2010 with a forecasted growth of 37% between 2014 and 2019. There is little research on e-liquid nicotine concentration from domestic manufacturers. However, limited research outside of the U.S. found wide inconsistencies between the labeled concentration of nicotine in e-liquids and the actual nicotine concentration. Methods: The seven most popular online manufacturers or distributors were identified. E-liquid samples of the five most popular flavors from each manufacturer were purchased in nicotine concentrations of 0 mg/ml and 18 mg/ml. Of the samples purchased (n=70), all were labeled as produced in the United States of America (USA). The researchers anonymized the samples before sending them to an independent university lab for testing. Results: The 35 e-liquid samples labeled 18 mg/ml nicotine measured between 11.6 and 27.4 mg/ml (M=18.7 SD=3.3) nicotine. The labeled 18 mg/ml samples measured as little as 35% less nicotine and as much as 52% greater nicotine. In the 35 samples labeled 0 mg/ml, nicotine was detected (>0.01 mg/ml) in 91.4% of the samples (Range = 0 to 23.9 mg/ml; M=2.9; SD=7.2). Six samples from two manufacturers labeled as 0 mg/ml were found to contain nicotine in amounts ranging from 5.7 mg/ml to 23.9 mg/ml. Conclusion: This study demonstrates the nicotine labeling inaccuracies present in current e-liquid solutions produced in the U.S. Incorrect labeling poses a significant risk to consumers and supports the recent regulation changes enacted by the FDA. Additional routine testing of nicotine concentrations should be conducted to evaluate the effectiveness of the regulations on future e-liquid production.
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45

Canals, Sotelo Jaume. "Tabaquisme i addicció a la nicotina. Relació amb el dolor de difícil control i l’Edmonton Classification System for Cancer Pain (ECS-CP)." Doctoral thesis, Universitat de Lleida, 2016. http://hdl.handle.net/10803/670018.

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Objectiu: Realitzar la traducció i la validació lingüística al català i al castellà de la “Quick User Guide” de l’Edmonton Classification System for Cancer Pain (ECS-CP). Metodologia: El procés de validació es va dur a terme en 3 fases. En la primera fase es va realitzar la traducció de la versió original en anglès al català i al castellà, per part de dos traductors independents. Aquest document va ser consensuat posteriorment amb l’equip investigador donant lloc a la primera versió (ECS-CP CATv1 i ECS-CP CAS v1). Posteriorment, aquesta versió va ser sotmesa a un procés de correcció gramatical (ECS-CP CAT v2 i ECS-CP CASv2). A partir d’aquesta segona versió, dos traductors independents van realitzar la retrotraducció al català i castellà, respectivament. Després d’haver conciliat diferències de criteri entre els traductors i l’equip investigador s’obtingué la tercera versió (ECS-CP CATv3 i ECS-CP CASv3). En la segona fase es va analitzar la llegibilitat i la intel·ligibilitat de la versió 3 i va donar lloc a la ECS-CP CATv4 i ECS-CP CASv4. L’estudi de la llegibilitat es va realitzar mitjançant l’aplicació de fórmules de llegibilitat a través del programa informàtic INFLESZ. Amb aquest programa es van analitzar l’Índex de Llegibilitat de Flesch-Szigriszt (IFSZ) i l’Índex de Fernández-Huertas. La intel·ligibilitat es va realitzar mitjançant el consens entre els traductors, l’equip investigador i els experts bilingües. Per al desenvolupament de la tercera fase es va seguir la metodologia utilitzada per Chewaskulyong B et al. en la validació del Palliative Performance Scale (PPS) de l’anglès al tailandès. Es van calcular diferents propietats psicomètriques com l’anàlisi de la validesa del contingut i l’anàlisi de la fiabilitat interna. Es va preparar un conjunt de 25 escenaris de casos clínics que es van adreçar a un grup de 20 clínics experts en l’àmbit de les cures pal·liatives i fi de vida de la regió sanitària de Lleida. Van respondre en 2 ocasions, separades 15 dies entre si. Abans de l’inici de l’estudi es va dur a terme una sessió de formació d’una hora de durada i, en acabar es va realitzar una enquesta entre els participants per tal de completar l’anàlisi qualitativa. Per al càlcul de la fiabilitat interna es va utilitzar el programa informàtic SPSS v20.0 i es va calcular el coeficient kappa per a variables ordinals. La “Quick User Guide” va acompanyada d’un document en què es defineixen els diferents termes utilitzats. De manera complementària i paral·lela es va realitzar una traducció de la mateixa per part dels mateixos traductors i els resultats es van consensuar amb els investigadors i experts lingüistes. També es va fer l’estudi de Llegibilitat i Intel·ligibilitat però no es va realitzar el procés de validació lingüística. La metodologia seguida per la segona part és la següent: La descripció de les variables contínues es va fer amb el valor de la mitjana i la seva desviació estàndard, i la mediana amb l’interval o rang interquantil. Les variables categòriques es van presentar amb percentatge (%). La comparació entre els diversos grups es va fer aplicant el test de chi-quadrat per a proporcions, test ANOVA per a comparació de mitjanes (amb anàlisi post hoc amb la correcció de Bonferroni) o el test no paramètric de Mann-Whitney de comparació de medianes (per a dos grups). S’ha acceptat una significació estadística per p < 0,05 La correlació entre els diversos valors dels factors analitzats es va realitzar segons la correlació no paramètrica de Spearman. Els pacients que van presentar valors superiors a EVA MAX de 7, es van definir com amb un “dolor sever”. Es va efectuar una anàlisi de regressió logística univariable i múltiple (selecció de variables per passos) per a detectar els factors que influeixen de forma independent per a pertànyer a aquest grup de pacients amb totes les variables disponibles en la primera visita. La propietat de discriminació de l’escala EDMONTON (i la modificada amb addicció a la nicotina) s’analitzarà amb la construcció de la corba ROC (ABC IC 95%). Per calcular els punts de tall per l’escala EDMONTON hem utilitzat arbres de classificació CHAID (Chi Square Automatic Interaction Detection). Els càlculs s’han realitzat amb el programa estadístic SPSS (v 20.0). Resultats: Per arribar a les ECS-CP CATv3 i ECS-CP CASv3 van ser necessàries diferents reunions entre els traductors, experts lingüistes i investigadors per consensuar els diferents canvis necessaris per elaborar la darrera versió. Els termes més significatius objecte de discussió van ser incidental pain (en anglès dolor menor), behaviour, cognitive impairment i distress que es van acceptar com a dolor incidental (dolor que apareix de manera sobtada i amb una intensitat gens menor), conducta, funció cognitiva i desconfort (en la versió catalana) i distrés (en la versió castellana). El resultat per a la versió en català de l’Índex de Llegibilitat de Flesch-Szigriszt va ser de 46.32 (una mica difícil i adient per a una població de batxillerat) i el resultat per a l’Índex de Fernández-Huertas va ser de 52 (bastant difícil, apte per a una població preuniversitaria). Els resultats per a la traducció de la definició de termes va ser de 52.65 (una mica difícil i adient per a una població de batxillerat) i de 57.72 (bastant difícil, per a una població preuniversitària), respectivament. El resultat per a la versió en castellà de l’Índex de Llegibilitat de Flesch-Szigriszt va ser de 54,61 (una mica difícil i adient per a una població de batxillerat) i el resultat per a l’ Índex de Fernández-Huertas va ser de 60.02 (dificultat normal i apte per a una població de 10-12 anys). Els resultats per a la traducció de la definició de termes va ser de 54.59 (dificultat una mica difícil i adient per a una població de batxillerat) i de 59.73 (bastant difícil i apte per a una població preuniversitària), respectivament. El coeficient Kappa promig per a la ECS-CP CATv4 va ser de 0,79 (grau d’acord bo) i de 0,83 per a l’ECS-CP CASv4 (grau d’acord molt bo). Pel que fa al coeficient Kappa promig per a cada component de l’ECS-CP, vam obtenir els següents resultats: Per a la versió catalana vam obtenir per a la N=0,69; I=0,69; P=0,65; A=0,94; C=0,88. Per a la versió castellana els resultats van ser per a la N=0,73; I=0,74;P=0,73; A=0,94; C=0,92). Dels col·laboradors només 17 van finalitzar el procés de validació. 2 no van completar la primera fase i, per tant, no van ser inclosos en la segona. Un tercer professional sanitari no va completar la segona fase i el seus resultats de la primera fase van ser exclosos de l’anàlisi estadística. Pel que fa als resultats de la segona fase, es van reclutar 211 pacients que complien amb els criteris d’inclusió (diagnosticats de neoplàsia en situació avançada i amb hàbit tabàquic ≥ 5 anys durant la seva vida) i 50 pacient en el grup control (també amb malaltia oncològica avançada però sense hàbit tabàquic). En el grup dels fumadors la mitjana d’edat va ser de 64 ± 14 anys mentre que els homes eren el 87.2% del total. En el grup control els resultats van ser 70,3± 14 anys i del 32%, respectivament. Totes dues variables amb un nivell de significació amb una p<0,001. les puntuacions obtingudes en els tests DN4 i CAGE són més elevades en el grup dels fumadors. En aquest grup també és major el percentatge de pacients que han precisat una ROP i que la MEDD final també és superior. En el grup dels fumadors (N=211), el grup dels pacients amb Fagestrom Major (F ≥ 7) són més joves i preferentment homes. Major prevalença de neoplàsia de pulmó. la variable A (addicció a l’alcohol) és més prevalent en el grup de F Major. També en la mostra de pacients fumadors (N=211) existeix un punt de tall = 6 que defineix un grup amb dolor menor (EVA ≤ 6 amb N = 75) i un grup amb dolor major (EVA ≥ 7 amb N = 136). Els pacients més joves presenten una EVA>6 amb més freqüència que els de més edat. També veiem com la intensitat del dolor es relaciona amb una major afectació en els paràmetres funcionals segons l’escala BPI. La intensitat del dolor (EVA>6) es relaciona amb el fet de presentar un menor % de millora prèvia a la nostra 1a valoració, una puntuació més elevada en el test DN4, en el MMDE i en el nombre de coanalgèsics emprats. Mitjançant el model multivariant de Regressió Logística Múltiple per a intensitat del dolor EVA > 6 (n=211), L’edat < 65 anys i el fagestrom > 6 són factors de risc de presentar dolor intens (EVA>6). Com més factors de risc (edat < 65 anys o F>6 ) presenten els pacients més gran és el % de pacients amb una intensitat del dolor amb EVA>6. Les puntuacions totals en l’ECS-CP són majors en el grup d’addictes a l’alcohol. També observem com la variable F (test de Fagestrom >6) és més prevalent en el grup d’addictes a l’alcohol. Els grup dels pacients amb un Fagestrom > 6 presenten una EVA màxima del dolor superior en la 1a visita i també un % inferior de milloria previa del dolor. També presenten puntuacions més elevades en el test de CAGE. Els fàrmacs analgèsics del tercer esglaó van ser utilitzats en 35 % dels casos abans de la nostra intervenció sent el fentanil transdèrmic l’analgèsic més emprat. Un cop el dolor va ser controlat, aquest grup de fàrmacs es van utilitzar en el 59 % i la morfina retardada es va prescriure en el 28 % dels casos. Els fàrmacs coanalgèsics més utilitzats pel control del dolor abans de la nostra intervenció van ser la gabapentina (18 %) i la pregabalina (5 %). Per ajudar a assolir un adequat control del dolor, els fàrmacs més utilitzats van ser la gabapentina (34 %) i els ADT (11 %). S’observa que tant en el grup global com en els subgrups en funció de la intensitat del dolor una disminució en l’ús dels analgèsics del segon esglaó i un increment en els del tercer esglaó, principalment en les formes retard i FAOs.
Objetivo: Realizar la traducción y la validación lingüística al Catalán y al Castellano de la “Quick User Guide” de la Edmonton Classification System for Cancer Pain (ECSCP). Metodología: El proceso de validación se desarrolló en 3 fases. En la primera fase se realizó la traducción de la versión original en inglés al catalán y al castellano, por parte de dos traductores independientes. Este documento fue posteriormente consensuado con el equipo investigador, dando lugar a la primera versión (ECS-CP CATv1 y ECS-CP CAS v1). Posteriormente, esta versión se sometió a un proceso de corrección gramatical (ECS-CP CAT v2 y ECS-CP CASv2). A partir de esta segunda versión, dos traductores independientes realizaron la retrotraducción del catalán y castellano al inglés. Después de la conciliación de diferencias de criterio entre los traductores y el equipo investigador se obtuvo la tercera versión (ECS-CP CATv3 y ECS-CP CASv3). En la segunda fase se analizaron la legibilidad y la inteligibilidad de la versión 3 dando lugar a la ECS-CP CATv4 y ECS-CP CASv4. El estudio de la legibilidad se llevó a cabo mediante la aplicación de fórmulas de legibilidad a través del programa informático INFLESZ. Con este programa se analizaron los Índice de legibilidad de Flesch-Szigriszt (IFSZ) y el Índice Fernández-Huertas. La inteligibilidad se realizó mediante el consenso entre los traductores, el equipo investigador i los expertos lingüistas. Para el desarrollo de la tercera fase se siguió la metodología utilizada por Chewaskulyong B et al. en la validación del Palliative Performance Scale (PPS) del inglés al tailandés. Se calcularon distintas propiedades psicométricas como el análisis de la validez del contenido y el análisis de la fiabilidad interna. Se preparó un conjunto de 25 escenarios de casos clínicos que se dirigieron a un grupo de 20 clínicos expertos en el ámbito de los cuidados paliativos y atención al final de la vida de la región sanitaria de Lleida. Respondieron en dos ocasiones, separadas entre sí por un espacio de tiempo de 15 días. Antes del inicio del estudio se realizó una sesión de formación de una hora de duración. Al acabar el estudio se realizó una encuesta entre los participantes para completar el análisis cualitativo. Para el cálculo de la fiabilidad interna se utilizó el programa informático SPSS v20.0 y se calculó el coeficiente kappa promedio para variables ordinales. La “Quick User Guide” se acompaña de un documento donde se definen los distintos términos utilizados. De manera complementaria y paralela se llevó a cabo su traducción por parte de los mismos traductores y el resultado se consensuó con los investigadores y los expertos lingüistas. También se realizó el estudio de legibilidad y de inteligibilidad pero no se realizó el proceso de validación lingüística. La metodología seguida para la segunda parte es la siguiente: La descripción de las variables continuas se realizó con el valor de la media y de su desviación estandar, y la media con el intérvalo o rango intercuartil. Las variables categóricas se muestran con el porcentaje (%). La comparación entre los diversos grupos se realizó aplicando el test de chi-cuadrado para proporciones, el test ANOVA para la comparación de medias (con análisis post hoc con la corrección de Bonferroni) o el test no paramétrico de Mann-Whitney de comparación de medias (para dos grupos). Se acepta una significación estadística para p < 0,05. La correlación entre los diversos valores de los factores analizados se realizó mediante la correlación no paramétrica de Spearman. Los pacientes que presentaron valores superiores a EVA MAX de 7, se definieron como “dolor severo”. Se efectuó un análisis de regresión logística univariable y múltiple (selección de variables por pasos) para la detección de los factores que influyen de manera independiente de pertenecer a este grupo de pacientes con todas las variables disponibles en la primera visita. La propiedad de discriminación de la escala EDMONTON (y la modificada con la adicción a la nicotina) se analizará con la construcción de la curva ROC (ABC IC 95%). Para el cálculo de los puntos de corte para la escala EDMONTON hemos utilizado árboles de clasificación CHAID (Chi Square Automatic Interaction Detection). Los cálculos se han realizado con el programa estadístico SPSS (v 20.0). Resultados: Para completar las ECS-CP CATv3 y ECS-CP CASv3 fueron necesarias diversas reuniones entre los traductores, los expertos lingüistas y los investigadores para consensuar los diferentes cambios necesarios para la elaboración de la última versión. Los términos más significativos objeto de discusión fueron incidental pain (en inglés dolor menor), behaviour, cognitive impairment y distress que se aceptaron como dolor incidental (dolor que aparece de manera súbita y con una intensidad nada menor), conducta, función cognitiva y Distrés (anglicismo frecuentemente utilizado en el ámbito sanitario). El resultado para la versión en catalán del Índice de legibilidad de Flesch-Szigriszt fue de 46.32 (un poco difícil y apto para una población de bachillerato) y el resultado del Índice de Fernández-Huertas fue 52 (bastante difícil y apto para una población de nivel preuniversitario). Los resultados para la traducción de la definición de términos fue de 52.65 (un poco difícil y apto para una población de bachillerato) y de 57.72 (bastante difícil y apto para una población preuniversitaria). El resultado para la versión en castellano del Índice de legibilidad de Flesch-Szigriszt fue de 54,61 (un poco difícil y que correspondería a una población de bachillerato) y el resultado para el Índice de Fernández-Huertas fue de 60.02 (apto para una población de 10-12 años). Los resultados para la traducción de la definición de términos fue de 54.59 (dificultad un poco difícil y apto para una población con un nivel de escolarización equivalente a bachillerato) y de 59.73 (bastante difícil y apto para una población preuniversitaria), respectivamente. El coeficiente Kappa para la ECS-CP CATv4 fue de 0,79 (grado de concordancia bueno) y de 0,83 para la ECS-CP CASv4 (grado de concordancia muy bueno). Para el coeficiente Kappa promedio de cada componente del ECS-CPCP, obtuvimos los siguientes resultados; Para la versión catalana obtuvimos para la N=0,69; I=0,69; P=0,65; A=0,94; C=0,88. Para la versión castellana, los resultados fueron para la N=0,73; I=0,74;P=0,73; A=0,94; C=0,92). De los colaboradores sólo 17 finalizaron el proceso de validación. Dos no completaron la primera fase y, por este motivo, no fueron incluidos en la segunda. Un tercer profesional sanitario no completó la segunda fase y sus resultados de la primera fase fueron excluidos del análisis estadístico. En relación a los resultados de la segunda fase, se reclutaros 211 pacientes que cumplían los criterios de inclusión (diagnóstico de enfermedad oncológica avanzada y con un hábito tabáquico ≥ 5 años durante su vida) y 50 pacientes en el grupo control (también con el diagnóstico de enfermedad oncológica pero sin el hábito tabáquico). En el grupo de los fumadores la media de edad fue de 64 ± 14 años mientras que los hombres serán el 87.2% del total. En el grupo control los resultados fueron de 70,3± 14 años y del 32%, respectivamente. Las dos variables con un nivel de significación con una p<0,001. Las puntuaciones obtenidas en los tests DN4 y CAGE son más elevadas en el grupo de los fumadores. En este grupo también es mayor el porcentaje de pacientes que han precisado una ROP y que la MEDD final también es superior. En el grupo de los fumadores (N=211), el grupo de los pacientes con Fagestrom Mayor (F ≥ 7) son más jóvenes y preferentemente hombres. Mayor prevalencia de neoplasia de pulmón. La variable A (adicción al alcohol) es más prevalente en el grupo de F Mayor. También en la muestra de pacientes fumadores (N=211) existe un punto de corte = 6 que define un grupo con dolor menor (EVA ≤ 6 con N = 75) y un grupo con dolor mayor (EVA ≥ 7 con N = 136). Los pacientes más jóvenes presentan una EVA>6 con más frecuencia que los de mayor edad. También observamos cómo la intensidad del dolor se relaciona con una mayor afectación en los parámetros funcionales según la escala BPI. La intensidad del dolor (EVA>6) se relaciona con el hecho de presentar un menor % de mejoría previa a nuestra primera valoración, una puntuación mayor en el test DN4, en el MMDE y en el número de coanalgésicos utilizados. Mediante el modelo multivariante de Regresión Logística Múltiple para una intensidad del dolor EVA > 6 (n=211), la edad < 65 años y el fagestrom > 6 son factores de riesgo de presentar dolor intenso (EVA>6). Cuantos más factores de riesgo (edad < 65 años o F>6 ) presentan los pacientes, mayor es el % de pacientes con una intensidad del dolor con EVA>6. Las puntuaciones totales en el ECS-CP son mayores en el grupo de adictos al alcohol. También observamos cómo la variable F (test de Fagestrom >6) es más prevalente en el grupo de los adictos al alcohol. El grupo de pacientes con un Fagestrom > 6 presentan una EVA máxima del dolor superior en la 1a visita y también un % inferior de mejoría previa del dolor. También presentan puntuaciones más elevadas en el test de CAGE. Los fármacos analgésicos del tercer escalón de la OMS se utilizaron en un 35 % de los casos antes de nuestra intervención siendo el fentanilo transdérmico el analgésico más utilizado en este grupo. Una vez el dolor fue controlado, este grupo de fármacos se utilizó en el 59 % de los pacientes siendo la morfina retardada la que se prescribió en el 28 % de los casos. Los fármacos coanalgésicos más utilizados para el control del dolor antes de nuestra intervención fueron la gabapentina (18 %) y la pregabalina (5 %). Para ayudar al control adecuado del dolor, los fármacos más utilizados fueron gabapentina (34 %) y los antidepresivos tricíclicos (11 %). Se observa que tanto en el grupo global como en los distintos subgrupos en función de la intensidad del dolor una disminución en el uso de los analgésicos de segundo escalón y un aumento de los fármacos del tercer escalón, principalmente de la formas retard y los FAOs.
Objectives: To translate the “Quick User Guide” of Edmonton Classification System for Cancer Pain (ECS-CP) into Catalan and Spanish. To validate the instrument in our population. Methodology: The process was designed in three phases. Phase I: two independents translators carried out the translation from original version in English into Catalan and Spanish. This provisional document was further consensuate with the investigation team leading to the first version (ECS-CP CATv1 and ECS-CP CAS v1). Afterwards this version suffered a grammatical adaptation (ECS-CP CAT v2 and ECS-CP CASv2). Then, two different independent translators carried out the backtranslation from Catalan and Spanish into English. After having sorted out criteria differences between translators and the investigation team the third version was set up (ECS-CP CATv3 i ECS-CP CASv3). In the second phase the readability and the intelligibility analysis of the third version was performed and the ECS-CP CATv4 and ECS-CP CASv4 were obtained. The study of the readability was performed through the application of readability formulas using the freeware INFLESZ. With this program the Flesch-Szigriszt readability index and the Fernandez-Huertas Index were obtained. The Intelligibility analysis was done with the agreement within translators, the investigation team amb the linguistic experts. In order to develop the third phase we follow the methodology used by Chewaskulyong B et al when they validated the Palliative Performance Scale (PPS) from English into Thai. Several different psychometric properties were calculated (content validity and internal reliability analysis). A set of 25 different scenarios with clinical cases were addressed to a group of 20 clinicians with expertise in the field of both palliative medicine and end-of-life care from the sanitary region of Lleida. They answered the scenarios twice with a gap of 15 days in between. Before the third phase was initiated we performed a formation session (one hour) and, when the whole process ended the participants were requested to fill a qualitative enquiry. In order to calculate the internal reliability we used the software package SPSS v20.0 and we obtained the kappa coefficient for ordinal variables. Together with the “Quick User Guide” there is a document with the definition of the terminology used. We also carried out the translation of the whole document and the results obtained were consensuate within the investigation team, translators and linguistic experts. We also performed the readability and intelligibility adequacy but not the linguistic validation. The methodology followed for the second part was: We used the mean and the standard deviation for the continuous variables. Categorical variables were expressed in percentage (%). The comparison between different groups was done with the Chi-squared test for proportions, the ANOVA test to compare means (with post hoc analysis with the Bonferroni correction) or the Mann-Whitney non-parametrical test to compare means between two groups. A level of statistical significance was accepted at p < 0,05 The correlation within different values of the factors analysed was carried out with the non parametrical Spearman test. Those patients with values of EVA MAX to 7, were defined as “severe pain”. A multivariate analysis was performed in order to detect those factors that influenced in an independent manner to belong to this group of patients with the data obtained in our first visit. The property of discrimination of the scale EDMONTON (and the modified one with the addiction to the nicotine) will be analyzed by the construction of the curve ROC (ABC IC 95 %). To calculate the cut-off point for the EDMONTON scale we used the CHAID (Chi Square Automatic Interaction Detection) classification. We used the SPSS (v 20.0) statistical package. Results: Several meetings within the translators, investigation team amb linguistic experts were necessary in order to consensuate the needed modifications before to achieve the ECSCP CATv3 and ECS-CP CASv3 versions. Several disagreements arose when dealing with the meaning of several words. Incidental pain (in English minor pain), behaviour, cognitive impairment and distress were translated as dolor incidental (pain that appears suddenly and with an important intensity), conducta, funció(n) cognitiva and distrés (English word widely used in the sanitary slang). The score for the Catalan version of the Flesch-Szigriszt Readability Index was 46.32 (somewhat difficult and ready for a high school literacy level population) and the score for the Fernandez-Huertas Index was of 52 (fairly difficult and ready for a preUniversitary literacy level population). The scores for the translation of the definition of terminology were of 52.65 (somewhat difficult and ready for a high school literacy level population) and of 57.72 (fairly difficult and ready for a pre-Universitary literacy level population) , respectively. The Flesch-Szigriszt Readability Index score for the Spanish version was 54,61 (somewhat difficult and ready for a high school literacy level population) and the Fernandez-Huertas Index score was 60.02 (good for a population of 10-12 years old). The scores for the definition of terminology were of 54,59 (somewhat difficult and ready for a high school literacy level population) and of 59.73 (fairly difficult and ready for a pre-Universitary literacy level population). The mean kappa coefficient for the ECS-CP CATv4 was of 0.79 (good level of agreement) and of 0.83 for the ECS-CP CASv4 (very good level of agreement). For the mean kappa coefficient for each item of the ECS-CP, the following results were obtained; For the catalan version, the result for the N=0,69; I=0,69; P=0,65; A=0,94; C=0,88. For the spanish version, the result for the N=0,73; I=0,74;P=0,73; A=0,94; C=0,92). From the 20 reporters recruited only 17 completed the study. Two did no complete the first phase so they were not included in the second phase) A third reporter did not complete the second phase so their data were excluded from the database analysis. In order to carry out with the second phase, we recruited 211 patients that met the inclusion criteria (advanced cancer and smokers > 5 years) and 50 patients in the group control (advanced cancer and non-smokers) Among the group of the smokers, the mean of age was 64 ± 14 years. Men were the 87.2% of the total. In the control group the results were 70,3± 14 years and the 32%, respectively. The level of significance was p<0,001. The scores obtained in the DN4 and CAGE questionnaires were higher in the smokers group. In this group it is significantly higher the % of patients that needed a ROP and the end MEDD in order to achieve a good pain control. In the smokers groups (N=211), patients with a Fagestrom score > 7 were men and younger and lung cancer was the most diagnosed tumour. The A variable (alcohol addiction) is more prevalent in the group with higher fagestrom score. Also, in the sample of smokers there is a cut-off point of VAS > 6. This point divides the sample in two different groups; the first one (N=75) with a VAS ≤ 6 and a second group (N=136) with a VAS > 6). Younger patients (age < 65 years) presents with a VAS >6 more frequently than older patients. Severity of pain relates directly with functional parameters according to the BPI scale. The intensity of pain (VAS > 6) correlates with the fact of having achieved a minor level of pain control prior to our first appointment, higher scores in the DN4 questionnaire, in the MMDE and in the number of coanalgèsics drugs used. By using the multivariate analysis, younger patients (age < 65 years) and Fagestrom score > 6 are considered a risk factor of presenting severe pain (VAS > 6). Total scores in the ECS-CP are higher among alcohol addicted patients. Addiction to nicotine defined with a fagestrom > 6 is also more prevalent among the alcohol addicted patients. Regarding the use analgesics, those belonging to the third step of the WHO analgesic ladder were prescribed in the 35% of the patients before our first intervention. Fentanil delivered through the transdermal route was the most used. Once pain was successfully controlled this group of drugs was used in the 59 % of patients and long acting morphine was prescribed in the 28% of patients. Among the coanalgèsics gabapentin (18%) and pregabalin (5%) were the most frequently prescribed before pain was under control. Once pain was controlled, gabapentin was prescribed in the 34% of the cases while tricyclic antidepressants were prescribed in the 11% of patients. In order to achieve a good pain control data suggest that second step analgesics were switched for third step analgesics, mainly with retard formulas and the FAOs.
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Klemperer, Elias Mushabac. "A Randomized Trial to Compare Switching to Very Low Nicotine Content Cigarettes Versus Reducing Cigarettes Per Day." ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/922.

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Smoking cigarettes is the most preventable cause of death in the US. Smokers are often unsuccessful at quitting because they are dependent. Reducing nicotine could be one way to reduce dependence. Currently, reducing cigarettes per day (CPD) is the most common strategy to reduce nicotine intake. However, some have proposed switching to very low nicotine content (VLNC) cigarettes to reduce nicotine and dependence. Both reducing CPD and switching to VLNC cigarettes aim to reduce nicotine but do so in different ways. I conducted a randomized trial to compare the degree to which switching to VLNC cigarettes vs reducing CPD 1) is more acceptable and 2) decreases dependence more among smokers not ready to quit. Sixty-eight adult smokers of ≥ 10 cigarettes/day who were not ready to quit smoked full nicotine study cigarettes ad-lib for 1 week (week 0). I provided all participants with nicotine replacement therapy (NRT) patches and instructions to gradually reduce over the next 4 weeks by either 1) switching to lower nicotine content VLNC cigarettes or 2) reducing the number of full nicotine CPD. I provided VLNC participants with their usual number of cigarettes throughout the study but cigarettes contained only 70% of their usual nicotine at week 1, 35% at week 2, 15% at week 3, and 3% at week 4. I provided CPD participants with full nicotine cigarettes throughout the study but only 70% of their usual number of cigarettes at week 1, 35% at week 2, 15% at week 3, and 3% at week 4. I instructed participants to attempt to smoke only study cigarettes and report use of all (study + non-study) cigarettes via nightly surveys. I used participants’ percent non-study cigarettes/day as a proxy for acceptability and the Nicotine Dependence Syndrome Scale as my primary measure of dependence. Participants completed self-report measures and provided breath and urine samples at weekly visits during the 5-week study period. I tested between-group differences, within-participant change over time, and group by time interactions using multi-level modeling. Switching to VLNC cigarettes was more acceptable than reducing CPD (F=5.0 p<.05). Acceptability declined over time for CPD participants as they were instructed to reduce more nicotine (F=42.2, p<.001) but this was not true for VLNC participants (F=29.5, p<.001). Dependence declined over time for both VLNC (F=10.5, p<001) and CPD (F=5.0, p<.01) participants but declined more over time for VLNC than CPD participants (F=3.2, p<.05). This is the first trial to directly compare switching to VLNC cigarettes vs reducing CPD. Large reductions were more acceptable and effective at decreasing dependence among participants who switched to VLNC cigarettes than those who reduced CPD when all were aided by NRT. My findings suggest that regulatory policy that promotes a gradual transition to VLNC cigarettes could be more acceptable and effective at decreasing dependence than the common strategy of reducing CPD. Furthermore, NRT-aided transitions to VLNC cigarettes could be a useful and acceptable component for clinical interventions to reduce nicotine dependence among smokers not ready to quit and thereby make it more likely for smokers to quit and succeed.
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47

Kirby, Seth, Elizabeth D. Cummins, Daniel J. Peterson, Leigh Kassem, and Russell W. Brown. "A Test of the Rewarding Versus Aversive Effects of Nicotine in Rats Neonatally Treated with Quinpirole." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/972.

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Aims: Neonatal quinpirole (a dopamine D2-like agonist) treatment to rats has been shown to increase dopamine D2 receptor sensitivity throughout the animal’s lifetime, and increased dopamine D2 sensitivity is a hallmark of schizophrenia. Schizophrenics are 3 to 4 times more likely to smoke than the normal population, but there is no delineating mechanism. Aim 1: Behaviorally test a rewarding versus averisve dose of nicotine in adolescent rats neonatally treated with quinpirole tested in a place preference paradigm; Aim 2: Analyze phosphorylated cylic AMP response element bidning protein (CREB) in brain areas that mediate drug reward. Methods: Rats were neonatally treated with quinpirole from postnatal days (P)1- 21. After two drug free preferene tests were given in a place preference shuttle box at P41-42, animals were conditioned with saline, a 0.6 or a 1.8 mg/kg free base dose of nicotine for eight consecutive days. A post-conditioning test was given 24 h after conditioning. Time in the paired and unpaired context were measured. Approximately 24 h after the post-condioning test, brain tissue was harvested, flash frozen, and later analyzed for pCREB in the dorsal and nucleus accumbens. Results: Results revealed that neonatal quinpirole enhanced the rewarding associative effects of the lower dose of nicotine compared to animals neonatally treated with saline and conditioned with the same dose of nicotine, which showed a slight place preference. Interestingly, although neonatal saline animals conditioned with the higher dose of nicotine demonstrated conditioned place aversion, neonatal quinpirole treated animals demonstrated no aversion to this same dose. Analyses for p-CREB will be presented. Conclusions: Rats neonatally treated with quinpirole demonstrate an enhancement of the rewarding properties of nicotine, but do not demonstrate an aversion to higher doses of nicotine. These data are congruent with recent self-administration data in our lab, and suggest that increases of dopamine D2 sensitivity may blunt aversive aspects of nicotine.
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48

Plaza-Zabala, Ainhoa 1982. "Involvement of the hypocretin/orexin system in the addictive properties of nicotine." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/116732.

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Hypocretin-1 and hypocretin-2, also known as orexin-A and orexin-B, are 2 neuropeptides that are exclusively expressed by a small subset of neurons of the lateral hypothalamic area. Despite their restricted expression pattern, hypocretin-containing axons project widely throughout the brain and exert their physiological functions acting on 2 G protein coupled receptors, hypocretin/orexin receptor-1 and hypocretin/orexin receptor-2. Initially, the hypocretin system was related to the regulation of sleep/wake cycles and feeding behavior. Nevertheless, a growing body of evidence has accumulated over the last decade indicating a role for these neuropeptides in drug addiction. In the present thesis, we have evaluated the involvement of hypocretin transmission in the addictive properties of nicotine, the main psychoactive component that sustains tobacco addiction, by using behavioral and biochemical approaches. Our results indicate that hypocretin peptides, mainly through their actions upon hypocretin receptor-1, influence the severity of nicotine withdrawal and modulate the relapse to nicotine-seeking after prolonged periods of abstinence. Given the importance of withdrawal and relapse on the pathophysiology of nicotine addiction, we propose hypocretin receptor-1 as a promising therapeutic target for the development of novel smoking cessation therapies.
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49

Oxley, Vanessa, and n/a. "The impact of becoming or wanting to become smokefree for Maori." University of Otago. Te Tumu - School of Maori, Pacific and Indigenous Studies, 2004. http://adt.otago.ac.nz./public/adt-NZDU20070502.151701.

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Since the introduction of tobacco into New Zealand, smoking and smoking related illnesses have become more prevalent in the Maori population than New Zealand's general population. The aim of the present research was to investigate smoking from a Maori perspective. It was hoped this information would provide a better understanding of how Maori can become smokefree. The present research also investigated a number of possible benefits that could be obtained by Maori through becoming smokefree. These benefits were analysed through Mason Durie's Whare Tapa Wha model, a Maori holistic health model. Semi-structured in-depth interviews were conducted with four Maori people, two of whom were current smokers and two who were ex-smokers. Common themes emerged from these interviews including the social aspect of smoking for Maori and the influence of the enviroment on smoking behaviour. Suggestions were given to illustrate how the social aspect of smoking and the cycle that subsequently develops can be broken. Using the Whare Tapa Wha model and the personal accounts given, the benefits of breaking such a cycle were discussed. Lastly, the importance of nurturing smokefree environments, especially Maori environments, was outlined. The notion of being positive about becoming smokefree and the need to celebrate giving up smoking were highlighted throughout this research.
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50

Ponzoni, L. "RUOLO DEI RECETTORI NICOTINICI CENTRALI NELL'ADDICTION' E NELLA 'DEPENDENCE' DA NICOTINA: POTENZIALE STRATEGIA FARMACOLOGICA DI NUOVI AGONISTI NICOTINICI PARZIALI." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/244857.

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Rationale 1: Cigarette smoking is one of the most serious health problems worldwide and people trying to stop smoking have high rates of relapse. Nicotine is the main psychoactive ingredient in cigarettes and its binding to neuronal nicotinic acetylcholine receptors (nAChRs) located in the mesolimbic areas induces reward (Picciotto and Kenney, 2013). Current first-line pharmacotherapies aiming at encouraging people to stop smoking include nicotine replacement therapy, bupropion hydrochloride and varenicline tartrate. The atypical antidepressant bupropion reduces the severity of nicotine craving during withdrawal, but its long-term beneficial effects on relapse are not clear (Hughes et al., 2007). Cytisine-related varenicline tartrate is a partial agonist of α4β2 and α6β2 nAChR subtypes and a full agonist of α7 and α3β4 nAChRs. Clinical trials indicate that varenicline is effective in decreasing relapse to smoking in humans (Cahill et al., 2011; Gonzales et al., 2006; Joreby et al., 2006; Tonstad et al., 2006; Zierler-Brown and Kyle, 2007) but adverse cardiovascular effects and/or neuropsychiatric events have recently been reported including depression, suicidal ideation, suicide attempts and completed suicide (Freedman, 2007; Moore et al., 2011; Singh et al., 2011). Aim 1: In search for new drugs that act on nicotine-induced dopamine release, firstly we tested the ability of new nicotinic partial agonists derivated from cytisine, 1,2-bis(cytisin-12-ul)ethane (CC4) and 1,4-bis(cytisin-12-yl)-2-butyne (CC26), compared to nicotine, cytisine and varenicline, to reduce nicotine-induced Conditioned Place Preference (CPP) in zebrafish, a promising animal model for rapidly screening new compounds to induce smoking cessation. Results 1: Our results demonstrated that CC4, CC26, cytisine and varenicline induced per se CPP with an inverted U-shaped dose-response curve similar to that of nicotine. However, when co-administered with the maximally effective dose of nicotine, they blocked its reinforcing effect. Since very little is known about the pharmacology of the native nicotinic subtypes expressed in zebrafish, we used binding and pharmacological experiments to identify the native nicotinic receptors in adult zebrafish brain by means of subtypes-selective antagonists. The results demonstrated that zebrafish brain expresses two distinct classes of nicotinic receptors: one containing the α7 subunit that binds [125I]-αbungarotoxin with high affinity and another that binds [3H]-epibatidine. We used also three antagonists α-conotoxin MII, methyllycaconitine (MLA) and dihydro-β-erythroidine (DhβE), selective respectively for α6β2, α7 and β2. Mecamilamine, a non selective antagonist, DhβE and MLA blocked the nicotine rewarding effect, demonstrating that nicotine exerted its addictive properties acting on α7 and β2 nAChRs. Since the results obtained in zebrafish looked promising, CC4 was also tested on rats, to verify if in this animal model it was effective in reducing nicotine rewarding effect. Our results demonstrated that CC4, like cytisine and nicotine, induced CPP and is ICV self-administered with an inverted-U dose response curve. Both models (CPP and ICV self-administration) showed that CC4 is per se slighty reinforcing, although to a lesser extent than nicotine. Moreover, in line with the fact that CC4 is a partial agonist, pre-treatment with non-reinforcing doses of CC4 significantly antagonized the rewarding effects induced by nicotine, both in CPP and in self administration task, without affecting motor functions. These findings indicate that this compound has a selective effect in reducing nicotine addiction-associated behaviours. Conclusions 1: Our results, obtained in zebrafish and in rats, demonstrated the possible development of CC4 or its derivatives as a new medication specific to tobacco smoking cessation with fewer side effects due to its lack of action on β4 nAChR subtypes. Rationale 2: In humans, however, the addiction is not just due to nicotine, but at least also to a complex of 4000 substances that constitute cigarette smoke. Recently electronic-cigarette (e-cigarette) has been introduced into the market with the purpose of mimic nicotine inhalation through traditional cigarette, whithout the negative effects of tobacco combustion. However, under now there are no long-term studies about the use of e-cigarette effects. In addition, the way in which nicotine is administered to experimental animals is very different from that used by humans: they do not mimic the route of administration used in the latter case, they are invasive and do not allow to study the effects of cigarette smoke compared to e-cigarette vapour (Cohen and George 2013). Aim 2: Thus, another aim of our study was to validate a rodent smoking model (tobacco smoke or e-cigarette vapour) and investigate the behavioural and biochemical changes after 7 weeks exposure. Male Balb/C mice were exposed to a mechanical ventilator delivering the smoke of 7 traditional cigarettes (cig) or e-cigarette vapour (e-cig) containing 5.6 mg of nicotine for three 30-minutes session/day for seven weeks. One hour after the last session, a group of animals was sacrified for biochemical assays and another group underwent mecamylamine precipitated or spontaneous withdrawal for behavioural analysis. Results 2: Mice submitted to cig or e-cig showed an increase in α4β2 nicotinic receptor subtypes in cerebral cortex, nucleus accumbens and hippocampus. To quantify the amount of nicotine intake and its metabolism, after 1, 4 and 7 weeks of exposure the urinary cotinine levels (the main nicotine metabolite) were quantified: Chronic intermittent exposure to cig or e-cig induces a similar increase of urinary cotinine concentrations (in a range of 700 ng/ml). During cig smoke or e-cig vapour exposure we monitored body weight and food intake: mice exposed to cig showed a significant progressive reduction across the weeks accompanied by a decrease in food intake while only a mild decrease in these parameters was shown in e-cig group. At the end of the exposure, we measured nicotine and cotinine levels in the brain of exposure animals: mice exposed to cig showed an increase in cotinine level, in contrast, mice exposed to e-cig showed an increase in cerebral nicotine level. To verify that our exposure method produces nicotine dependence we precipitated withdrawal syndrome with mecamylamine (1 mg/kg, s.c.), a non selective antagonist: mice submitted to cig or e-cig showed a significant increase in withdrawal-precipitated symptoms. However e-cig group showed a less severe withdrawal syndrome. There was also a reduction of motor function only in cig exposed mice probably due to the presence of severe signs. Finally we monitored spontaneous withdrawal syndrome from 24 hours to 90 days after the end of exposure. In comparison with the control group, both groups exposed to cig or e-cig showed impaired spatial memory (evaluated using the spatial object recognition task) and a progressive increase in anxiety-like behavior (evaluated using elevated plus maze test and marble burying test) starting from 24 hour to at least 90 days after spontaneous withdrawal. Finally, after 60 days e-cig animals and after 90 days cig group, showed a depressive-like behaviour, measured with Tail Suspension test and Sucrose Preference test. Conclusions 2: In conclusion, we propose an innovative procedure for investigating the short- and long- term alterations induced by exposure to tobacco smoke and, for the first time, we describe the short- and long- term effects of e-cig. Finally, this rodent model is also most suitable for testing new compounds for smoking cessation, such as CC4, whose effectiveness has already been tested on zebrafish and rats. Future: We propose to investigate the effect of CC4 on nicotine dependence in both cig and e-cig exposed animals. 1. Picciotto MR, Kenny PJ; “Molecular mechanisms underlying behaviors related to nicotine addiction” Cold Spring Harbor perspectives in medicine 3: a012112, 2013 2. Hughes JR, Stead LF, Lancaster T; “Antidepressants for smoking cessation” The Cochrane database of systematic reviews CD000031, 2007 3. Cahill K, Stead LF, Lancaster T; “Nicotine receptor partial agonists for smoking cessation” The Cochrane database of systematic reviews CD006103, 2011 4. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; “Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial” JAMA: the journal of the American Medical Association 296: 47-55, 2006 5. Joreby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; “Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial” JAMA: the journal of the American Medical Association 296: 56-63, 2006 6. Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR; “Effects of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial” JAMA: the journal of the American Medical Association 296: 64-71, 2006 7. Zierler-Brown SL, Kyle JA; “Oral varenicline for smoking cessation” The Annals of pharmacotherapy 41: 95-99, 2007 8. Freedman R; “Exarbation of schizophrenia by varenicline” The American journal of psychiatry 164: 1269, 2007 9. Moore TJ, Furberg CD, Glenmullen J, Maltsberger JT, Singh S; “Suicidal behavior and depression in smoking cessation treatments” PloS one 6: e27016, 2011 10. Singh S, Loke YK, Spangler JG, Furberg CD; “Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis” CMAJ: Canadian Medical Association journal = journal de l’Association medicale canadienne 183: 1359-1366, 2011 11. Cohen A, George O; “Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking” Font Psychiatry doi: 10.3389/fpsyt.2013.00041, 2013
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