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1
Truchanowicz, Ewa G. "Prepulse reactivity in prepulse inhibition." Thesis, Swansea University, 2010. https://cronfa.swan.ac.uk/Record/cronfa42605.
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Prepulse inhibition (PPI) is a popular paradigm in sensorimotor gating research. In healthy individuals the weak lead stimulus (i.e., the prepulse) presentation results in a reduction in the startle probe (pulse) elicited response. The motor responses to the prepulses (prepulse reactivity, PPER) were until recently largely ignored in PPI research. There are conflicting reports about prepulse reactivity and startle response modification (SRM) associations; and personality factors relevant to SRM have not been previously examined in prepulse reactivity context. Healthy participants were drawn from university student and staff population. Three paradigms were used: unpredictable stimulus onset, predictable stimulus onset and conscious stimulus processing. The stimuli consisted of 80, 85 & 90dB prepulses and 115dB startle probe separated by 140ms inter-stimulus interval (onset to onset asynchrony). The inter-trial intervals varied between the studies. Startle responses were measured as eye blinks and recorded using surface EMG. All motor responses were quantified according to the same set of rules. Prepulse-elicited motor responses reliably appeared in all the studies and were distinct from spontaneous EMG. Some PPER characteristics exhibited stimulus intensity dependence further proving PPER validity as stimulus-driven response. Prepulse reactivity exhibited significant associations with startle response modification. PPER was a stable tendency; individuals either consistently responded to the weak lead stimuli or did not. Two types of startle response modification appeared under the conditions assumed to elicit maximal inhibition only: classical inhibition (as expected) and paradoxical prepulse facilitation. These appeared in motor responses and in conscious stimulus processing. The propensity towards the paradoxical prepulse facilitation was reduced by efficient prepulse inhibition. PPER and SRM had limited associations with personality factors, sex, or age. The predictable stimulus onset paradigm however highlighted the associations of the defensive startle response and its modification with fear and anxiety. Increased emotionality, regardless of its valence, proved detrimental to sensorimotor gating.
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Parker, Stephen David. "The effects of attention and stimulus onset asynchrony on the relationship between prepulse inhibition of the startle-eyeblink and prepulse-rating inhibition /." [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16834.pdf.
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Tanner, Lisa. "Effects of early acoustic stimulation on prepulse inhibition in mice." Scholar Commons, 2003. https://scholarcommons.usf.edu/etd/1490.
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The purpose of this study was to determine the effects of an atypical pattern of early acoustic stimulation on auditory development. Previous human research suggests that the acoustic environment of pre-term human infants in the Neonatal Intensive Care Unit (NICU) negatively affects some aspects of auditory development. Animal research suggests that premature auditory stimulation interrupts auditory development. Because mice are born before their auditory systems are developed, they make an excellent model for research on fetal and postnatal plasticity of the auditory system. The premature auditory state of newborn mice is similar to that of the NICU pre-term infant, albeit, natural for mice
C57 mouse pups were exposed to an augmented acoustic environment (AAE) of a nightly 12-hour regiment of 70 dB SPL noise burst, beginning before age 12 days (onset of hearing) and lasting for one month. The prepulse inhibition (PPI) of mice exposed to the AAE was compared to that of non-exposed mice to observe short-term and long-term effects. Results showed that the prepulse inhibition of the AAE exposed mice did not differ significantly from that of the non-exposed mice. However, it is possible that the measurement used, PPI, may not have been appropriate or that the AAE may not have been an appropriate simulation of the NICU environment.
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Poje, Albert Buddy Filion Diane L. "The effects of multiphasic prepulse stimuli on attentional modulation of prepulse inhibition of the acoustic startle eyeblink response." Diss., UMK access, 2007.
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Thesis (Ph. D.)--Dept. of Psychology. University of Missouri--Kansas City, 2007."A dissertation in psychology." Advisor: Diane L. Filion. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed July 16, 2008. Includes bibliographical references (leaves 109-118). Online version of the print edition.
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Varty, Geoffrey Brian. "Investigations into prepulse inhibition : a proposed in vivo model for schizophrenia." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309718.
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Ralph, Rebecca Jeanette. "Dopamine modulation of prepulse inhibition and locomotor behavior in knockout mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3001269.
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Swonger, Jessica M. "Prepulse Inhibition of the Startle Reflex in Forebrain Oxytocin Receptor Knockout Mice." Kent State University Honors College / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1304360430.
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O'steen, Jennifer Robin. "Prepulse Inhibition and the Acoustic Startle Response in Nine Inbred Mouse Strains." Scholar Commons, 2003. https://scholarcommons.usf.edu/etd/1443.
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This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans.
Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration.
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Maple, Amanda M., Katherine J. Smith, Marla K. Perna, and Russell W. Brown. "Neonatal Quinpirole Treatment Produces Prepulse Inhibition Deficits in Adult Male and Female Rats." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/947.
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We have shown that repeated neonatal quinpirole (QUIN; a dopamine D2-like receptor agonist) treatment in rats produces long-lasting supersensitization of dopamine D2 receptors that persists into adulthood but without producing a change in receptor number. The current study was designed to analyze the effects of neonatal QUIN on auditory sensorimotor gating as measured through prepulse inhibition (PPI). Male and female Sprague–Dawley rats were neonatally treated with QUIN (1mg/kg) or saline from postnatal days (P)1–21. At P60, the number of yawns was recorded for a 1h period in response to an acute QUIN (1mg/kg) injection as yawning is a D2-like receptor mediated behavioral event. Five days later, rats began (PPI) behavioral testing in two phases. In phase I, three different prepulse intensities (73, 76, and 82dB) were administered 100-ms before a 115dB pulse on 10 consecutive days. In phase II, three different interstimulus intervals (ISI; 50, 100, and 150ms) were inserted between the 73 or 76dB prepulse and 115dB pulse over 10 consecutive days of testing. A PPI probe trial was administered at the end of each phase after an acute 100μg/kgi.p. injection of QUIN to all animals. Replicating previous work, neonatal QUIN enhanced yawning compared to controls, verifying D2 receptor supersensitization. Regarding PPI, neonatal QUIN resulted in deficits across both phases of testing persistent across all testing days. Probe trial results revealed that acute QUIN treatment resulted in more robust PPI deficits in neonatal QUIN animals, although this deficit was related to prepulse intensity and ISI. These findings provide evidence that neonatal QUIN treatment results in deficits of auditory sensorimotor gating in adulthood as measured through PPI.
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Kedzior, Karina Karolina. "Chronic cannabis use and attention-modulated prepulse inhibition of the startle reflex in humans." University of Western Australia. School of Medicine and Pharmacology, 2004. http://theses.library.uwa.edu.au/adt-WU2004.0027.
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Background. Various studies show that cannabis use alters attention and cognitive functioning in healthy humans and may contribute to development of schizophrenia or worsening of pre-existing psychosis. However, the impact of cannabis use on brain function in humans is not well understood. Schizophrenia is associated with a deficit in prepulse inhibition (PPI), the normal inhibition of the startle reflex by a non-startling stimulus (prepulse), presented before the startle stimulus at short time intervals (lead-time intervals). Such PPI deficit is thought to reflect a sensorimotor gating dysfunction in schizophrenia. PPI is also modulated by attention and PPI reduction in schizophrenia is observed when patients are asked to attend to, not ignore, the stimuli producing PPI. The aim of the current study was to investigate the association between self-reported chronic cannabis use and attentional modulation of PPI in healthy controls and in patients with schizophrenia. Furthermore, the association between cannabis use and other startle reflex modulators, including prepulse facilitation (PPF) of the startle reflex magnitude at long lead-time intervals, prepulse facilitation of the startle reflex onset latency and habituation of the startle reflex magnitude, were examined. Method. Auditory-evoked electromyographic signals were recorded from orbicularis oculi muscles in chronic cannabis users (29 healthy controls and 5 schizophrenia patients) and non-users (22 controls and 14 patients). The data for 36 participants (12 non-user controls, 16 healthy cannabis users, and eight non-user patients) were used in the final analyses and the patient data were used as a pilot study, because relatively few participants met the rigorous exclusionary criteria. Participants were instructed to attend to or to ignore either the startle stimuli alone (70 100 dB) or prepulse (70 dB) and startle stimuli (100 dB) separated by short lead-time intervals (20 200 ms) and long lead-time intervals (1600 ms). In order to ignore the auditory stimuli the participants played a visually guided hand-held computer game. A pilot study showed that the response component of playing the game had no effects on attentional modulation of the startle reflex magnitude and onset latency. Results. Relative to controls, cannabis use in healthy humans was associated with a reduction in PPI similar to that observed in schizophrenia while attending to stimuli, and with an attention-dependent dysfunction in the startle reflex magnitude habituation. While ignoring the stimuli there were no statistical differences in PPI between cannabis users and controls, although PPI in cannabis users tended to differ from that of the patients. The reduction in PPI in cannabis users was correlated with the increased duration of cannabis use, in years, but not with the concentration of cannabinoid metabolites in urine or with the recency of cannabis use in the preceding 24 hours. Furthermore, cannabis use was not associated with any differences in PPF, onset latency facilitation, and startle reflex magnitude in the absence of prepulses. The accuracy of self-reports of substance use was also investigated in this study and was found to be excellent. In addition, the study examined the validity of the substance use module of the diagnostic interview, CIDI-Auto 2.1, which was found to be acceptable for cannabis misuse diagnoses (abuse and/or dependence). Finally, cannabis dependence was found to be associated with more diagnoses of mental illness other than schizophrenia (mainly depression). Conclusions. The results of the current study suggest that chronic cannabis use is associated with schizophrenia-like deficit in PPI in otherwise healthy humans. This PPI reduction is associated with attentional impairment rather than a global sensorimotor gating deficit in healthy cannabis users.
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Kędzior, Karina Karolina. "Chronic cannabis use and attention-modulated prepulse inhibition of the startle reflex in humans /." Connect to this title, 2004. http://theses.library.uwa.edu.au/adt-WU2004.0027.
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PARDU, ALESSANDRA. "Prepulse inhibition come strumento diagnostico per lo studio del comportamento impulsivo-aggressivo nella schizofrenia." Doctoral thesis, Università degli Studi di Cagliari, 2016. http://hdl.handle.net/11584/266685.
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Sensorimotor gating is a perceptual process aimed at filtering out irrelevant information. In humans and animal models, this function can be operationally measured through the prepulse inhibition (PPI) of the acoustic startle reflex. Notably, PPI deficits are associated with numerous neuropsychiatric conditions characterized by gating disturbances and personality aggressive traits, including schizophrenia and Tourette syndrome. Nevertheless, the mechanism underlying the physiopathology is poor understood, principally by the lack of valid animal models. Given the genetic and environmental interplay in schizophrenia background onset, we tested a (endo)phenotype of schizotypal behavior associated with aggression, provided by a MAO-A deficient mice line subjected to early psychosocial stress. Interestingly, these animals represent an isomorphic model of human condition of MAO-A polymorphism, related to antisocial personality and increased aggression. We investigated drug sensibility on sensorimotor gating function across different rat and mice strains to elicit differences due to genetic background in PPI response. Furthermore, we tested MAO-A deficient mice mutant with resident-intruder test to asses early stress impact on aggressive and antisocial behavior.
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Tanner, Lisa. "Effects of early acoustic stimulation of prepulse inhibition in mice [electronic resource] / by Lisa Tanner." University of South Florida, 2003. http://purl.fcla.edu/fcla/etd/SFE0000070.
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Professional research project (Au.D.)--University of South Florida, 2003.Title from PDF of title page.
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Includes bibliographical references.
Text (Electronic thesis) in PDF format.
ABSTRACT: The purpose of this study was to determine the effects of an atypical pattern of early acoustic stimulation on auditory development. Previous human research suggests that the acoustic environment of pre-term human infants in the Neonatal Intensive Care Unit (NICU) negatively affects some aspects of auditory development. Animal research suggests that premature auditory stimulation interrupts auditory development. Because mice are born before their auditory systems are developed, they make an excellent model for research on fetal and postnatal plasticity of the auditory system. The premature auditory state of newborn mice is similar to that of the NICU pre-term infant, albeit, natural for mice C57 mouse pups were exposed to an augmented acoustic environment (AAE) of a nightly 12-hour regiment of 70 dB SPL noise burst, beginning before age 12 days (onset of hearing) and lasting for one month.
ABSTRACT: The prepulse inhibition (PPI) of mice exposed to the AAE was compared to that of non-exposed mice to observe short-term and long-term effects. Results showed that the prepulse inhibition of the AAE exposed mice did not differ significantly from that of the non-exposed mice. However, it is possible that the measurement used, PPI, may not have been appropriate or that the AAE may not have been an appropriate simulation of the NICU environment.
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Kerkhoff, Jane-Elisabeth. "Isolation-rearing induced deficits in prepulse inhibition of acoustic startle : how reliable is this phenomenon?" Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312147.
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Brody, Suzanne Amy. "Role of the Group I metabotropic glutamate receptors in prepulse inhibition of the startle response /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3099921.
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Gill, Wesley D., J. D. Wherry, Katherine C. Burgess, and Russell W. Brown. "Prepulse Inhibition Deficits in the Neonatal Quinpirole Model of Schizophrenia: Epigenetic Evidence and Sex Differences." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/969.
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Neonatal quinpirole (QUIN; dopamine D2/D3 agonist) administered from postnatal days (P)1-21 results in an increase of dopamine D2 receptor sensitivity, similar to schizophrenia and is now an established rodent model of schizophrenia. The day after birth, male and female Sprague-Dawley rats were given a daily 1 mg/kg injection of either QUIN or saline from P1-21. One subset of these animals were behaviorally tested on PPI, referred to as first generation (F0). A different subset of animals were allowed to reach adult age (P60) and female and male QUIN-treated pairs from separate litters were bred. Their offspring were also used as subjects (F1 generation). Prepulse inhibition (PPI) is a measure of sensorimotor gating reduced in individuals diagnosed with schizophrenia. Trial types were defined as prepulse trials (73, 76, 82dB), startle stimuli trials (120 dB), or no stimulus (70 dB white noise; no prepulse or pulse). Animals were tested for six consecutive days and given an ip saline injection 10 min before testing, followed by testing for another six consecutive days and given an ip nicotine (0.5 mg/kg free base) or saline injection 10 min before testing. PPI testing for F0 generation animals occurred between P35-46, and testing for F1 generation animals occurred between P44-55. In one subset of generation F1 animals, rats were ip injected with a 0.1 mg/kg dose of quinpirole and immediately observed for 60 min and the number of yawns were recorded at P60. Yawning is a behavioral event mediated by the dopamine D2 receptor. Results revealed that neonatal QUIN resulted in PPI deficits throughout the six days of testing in the F0 generation regardless of the prepulse stimulus, but females demonstrated a less robust PPI deficit as compared to males. Nicotine given during the final 6 days of testing partially alleviated the PPI deficits in both males and females. The F1 generation also demonstrated PPI deficits, but the impairment was only in males and dissipated by day 6. Nicotine did not affect PPI in these animals. Finally, F1 generation rats demonstrated a robust increase in yawning compared to controls, demonstrating an increase in D2 receptor sensitivity. Brain tissue is being analyzed for changes in the dopamine D2 receptor signaling pathway.
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Gill, Wesley. "Behavioral and Neurobiological Evidence of Epigenetic Transmission in the Neonatal Quinpirole Rodent Model of Schizophrenia." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etd/3719.
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Quinpirole is a dopamine D2 receptor agonist that if administered to rats from postnatal day (P)1-21 results in increased dopamine D2 receptor sensitivity throughout the animal’s lifetime. This increase in receptor sensitivity is consistent with schizophrenia. This model has additional consistencies with human schizophrenia, including sensorimotor gating deficits, enhanced behavioral and neurobiological responses to nicotine, and protein alterations consistent with the disorder. In this study, a second generation of the neonatal quinpirole (NQ) rodent model was created to investigate if long term changes caused by NQ treatment would be passed to offspring. NQ treated rats were mated and their offspring left untreated. To investigate if dopamine D2 receptor hypersensitivity was transmitted from the first to the second generation of the model, yawning behavior was assayed after acute quinpirole treatment. Prepulse inhibition (PPI) is a test of sensorimotor gating, and PPI testing was performed on adolescent second generation rats. Behavioral sensitization and conditioned place preference to nicotine (0.5 mg/kg and 0.6 mg/kg respectively) were examined in adolescence in both generations of the model. Several neurobiological assays were performed in both nicotine naïve and animals sensitized to nicotine (0.5 mg/kg) in order to investigate consistencies with the NQ model, which has shown enhanced responses to nicotine. These include enzyme linked immunosorbent assays (ELISAs) for brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB), as well as quantitative PCR (qPCR) to quantify messenger RNA (mRNA) of regulator of G-protein signaling 9 (rgs9). Results indicated that second generation rats of NQ-treated rats demonstrated increased yawning behavior in response to acute quinpirole treatment. PPI deficits and enhanced behavioral responses to nicotine were also observed. Increased BDNF expression was observed in the nucleus accumbens following nicotine sensitization, consistent with past work in first generation NQ-treated rats. CREB expression was also increased in both generations of the model, an effect linked to alterations in PPI and other schizophrenia-like symptomology. Rgs9 expression was generally unaltered in either generation of the model. This study provides basis for utilization of a second generation of the NQ model to study epigenetic influences in schizophrenia and drug abuse vulnerability.
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Gill, Wesley. "Behavioral and Neurobiological Evidence of Epigenetic Transmission in the Neonatal Quinpirole Rodent Model of Schizophrenia." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etd/3719.
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Quinpirole is a dopamine D2 receptor agonist that if administered to rats from postnatal day (P)1-21 results in increased dopamine D2 receptor sensitivity throughout the animal’s lifetime. This increase in receptor sensitivity is consistent with schizophrenia. This model has additional consistencies with human schizophrenia, including sensorimotor gating deficits, enhanced behavioral and neurobiological responses to nicotine, and protein alterations consistent with the disorder. In this study, a second generation of the neonatal quinpirole (NQ) rodent model was created to investigate if long term changes caused by NQ treatment would be passed to offspring. NQ treated rats were mated and their offspring left untreated. To investigate if dopamine D2 receptor hypersensitivity was transmitted from the first to the second generation of the model, yawning behavior was assayed after acute quinpirole treatment. Prepulse inhibition (PPI) is a test of sensorimotor gating, and PPI testing was performed on adolescent second generation rats. Behavioral sensitization and conditioned place preference to nicotine (0.5 mg/kg and 0.6 mg/kg respectively) were examined in adolescence in both generations of the model. Several neurobiological assays were performed in both nicotine naïve and animals sensitized to nicotine (0.5 mg/kg) in order to investigate consistencies with the NQ model, which has shown enhanced responses to nicotine. These include enzyme linked immunosorbent assays (ELISAs) for brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB), as well as quantitative PCR (qPCR) to quantify messenger RNA (mRNA) of regulator of G-protein signaling 9 (rgs9). Results indicated that second generation rats of NQ-treated rats demonstrated increased yawning behavior in response to acute quinpirole treatment. PPI deficits and enhanced behavioral responses to nicotine were also observed. Increased BDNF expression was observed in the nucleus accumbens following nicotine sensitization, consistent with past work in first generation NQ-treated rats. CREB expression was also increased in both generations of the model, an effect linked to alterations in PPI and other schizophrenia-like symptomology. Rgs9 expression was generally unaltered in either generation of the model. This study provides basis for utilization of a second generation of the NQ model to study epigenetic influences in schizophrenia and drug abuse vulnerability.
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Whicker, Wyatt, W. Drew Gill, and Russell W. Brown. "DISCOVERY OF A NOVEL ANTI-NEUROINFLAMMATORY TREATMENT FOR AUDITORY SENSORIMOTOR GATING IN TWO RODENT MODELS OF SCHIZOPHRENIA." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/204.
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Schizophrenia is primarily treated with the use of antipsychotic medications. However, antipsychotics used have severe, dose-dependent side effects in schizophrenia patients. Therefore, there is a need for new adjunctive drugs that lower the effective dose of first line schizophrenia drugs and improve patient symptoms. Neuroinflammation is associated with microglial activation in schizophrenia, and increased tumor necrosis factor-alpha (TNF) has shown to be associated with Metabolic Syndrome in schizophrenia patients. A newly developed anti-neuroinflammatory, PD2024, reduces TNF-alpha action in vitro and in vivo, and has been shown to be well-tolerated in rat and dog studies with no adverse effects. The purpose of this research is to evaluate the effect of PD2024 in two well-defined schizophrenia models in rats. The neonatal quinpirole model has been established through administration of the dopamine D2-like agonist quinpirole (NQ) or saline control (NS) postnatally from days 1-21. NQ treatment results in increases of dopamine D2 receptor sensitivity throughout the animal’s lifetime without changing receptor number, mimicking a hallmark of schizophrenia. The polyinosinic:polycytidylic acid (Poly I:C) model is based on mimicking an increase immune response during early brain development, which has been shown to increase the prevalence of schizophrenia. Poly I:C (2 mg/kg) was administered during the neonatal period at postnatal days (P)5-7 to produce this effect. Both models were given PD2024 at 10mg/kg orally through the diet from P30-67. Prepulse inhibition (PPI) was used to test sensorimotor gating deficits in the rats. PPI has past research showing its use as a quantitative phenotype for evaluating schizophrenia-associated behavioral and neurobiological deficits. In our PPI test, rats are exposed to three different, randomly ordered noise trials. The trials included a pulse trial with a 120-decibel startle pulse, a prepulse trial with an auditory click at 73, 76, or 82-decibels, and a no stimulus trial without any additional noise. The rats were given 25 randomized trials, comprised of 5 pulse, 15 prepulse (5 each of 73, 76, and 82dB) and 5 no stimulus trials. Background noise was 70dB, and the rats were tested during adolescence (days 45-46) and adulthood (60-65). In NQ adolescent rats, PPI was significantly improved in the PD2024-treated compared to NQ controls. NQ-PD2024 and NS rats were statistically equivalent throughout the trials. These results were reflected in the NQ adult model as well. The Poly I:C adolescents treated with PD2024 also demonstrated improved PPI performance compared to Poly I:C controls. This improvement was also shown in the adult Poly I:C rats. Overall, the PPI deficits in both models improved between 15 to 30% in adolescence and adulthood. These results indicate that PD2024 is effective in treating schizophrenia-associated behaviors.
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Möller, Marisa. "Oxidative status in rats exposed to social isolation rearing : behavioral pharmacology studies and relevance for schizophrenia / Marisa Moller." Thesis, North-West University, 2009. http://hdl.handle.net/10394/5091.
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PURPOSE: Psychotic (positive) symptoms are the most distinctive feature of schizophrenia, although negative symptoms such as emotional flattening, social withdrawal and cognitive disturbances are the most treatment resistant manifestation of the illness. Schizophrenia is a progressive degenerative illness that has been causally linked to environmental and neurodevelopmental factors, as well as dysfunctional redox balance. Validated animal models are useful in identifying and studying novel neurobiological targets for neuropsychiatric illnesses. Post weaning social isolation rearing (SIR) in rats has been proposed to model the neurodevelopmental aspects of schizophrenia. We validated the SIR model with respect to effects on sensorimotor gating and social interaction, deficits of which are core symptoms of schizophrenia. Following this, effects on the levels of oxidative stress were determined in the frontal cortex and striatum of rats exposed to SIR, two brain regions strongly implicated in the pathology of schizophrenia. Finally, in order to more closely relate these bio-behavioural changes to the human condition, we studied the overall effect of sub-chronic treatment with the atypical antipsychotic, clozapine, on the above described behavioural and neurochemical parameters.
METHODS: Male Sprague-Dawley (SD) rats (10 rats/group) were used. In a non-treatment arm, four groups of rats were randomly separated at weaning and exposed to either 8 weeks SIR or 8 weeks social rearing. At the respective time point of 8 weeks two groups were subjected to behavioural testing of mean startle amplitude (at 120dB) and percentage prepulse inhibition (%PPI) of the acoustic startle (AS) reflex (at 72, 76, 80 and 86dB prepulse), and various social interactive and self-directed behaviours were accessed using the open field test (OFT). The remaining two groups were sacrificed at 8 weeks and brain tissue was harvested for analysis of superoxide dismutase activity, oxidized (GSSG) versus reduced (GSH) glutathione ratio, and levels of lipid peroxidation, in the frontal cortex and striatum. In the treatment arm, consisting out of eight groups of animals, four groups of SIR rats received either saline or clozapine (5mg/kg i.p.) for the last 11 days of SIR. The remaining four groups were socially reared and also received either saline or clozapine treatment as above. At 8 weeks, four groups were subjected to behavioural testing as described above and a parallel neurochemical study was performed using the same layout as above, except that after the 8 weeks, neurochemical redox analysis were done as described above. Mixed statistical modelling with repeated measures and appropriate post hoc tests were used to access the effects of SIR with and without treatment on PPI and mean startle. Social interaction in SIR and socially reared animals, with and without treatment, was analyzed using 1-way ANOVA with suitable post hoc testing. Mixed linear models with repeated measures and appropriate post hoc tests were used for analysis of the redox data in SIR and socially reared animals, with and without treatment.
RESULTS: In the non-treatment arm, %PPI was significantly reduced in SIR versus socially reared rats. Deficits in various social interactive behaviours were observed in SIR versus group-housed rats, as well as increased locomotor activity and self-grooming. Superoxide dismutase activity and oxidized versus reduced glutathione ratio were significantly decreased, together with a significant increase in products of lipid peroxidation, in isolation reared versus socially reared rats.
Following clozapine treatment, %PPI in isolates was significantly elevated by clozapine versus saline treatment (i.e. reversed the effect of SIR). %PPI was unaltered in socially reared animals receiving either treatment. As with the non-treatment group, social interactive behaviours were significantly impaired in isolates receiving saline, while locomotor activity and self-grooming were increased. SIR rats receiving only saline showed similar altered redox state as the non-treatment groups, while clozapine treatment effectively reversed deficits in %PPI, aberrant social behaviours and redox alterations in the SIR rats, with limited to no effects in the socially reared controls.
CONCLUSION: SIR thus significantly disrupts sensorimotor gating and social behaviours in male Sprague-Dawley rats, while at the same time evokes a significant disruption of redox state in both the frontal cortex and striatum of these animals, with distinct evidence for increased oxidative stress in these brain regions. Importantly, both altered behaviour and redox state are reversed by sub-chronic clozapine treatment. SIR is therefore a useful, non-lesion and non-pharmacological neurodevelopmental animal model of schizophrenia that presents with robust face, predictive and possibly construct validity for schizophrenia.Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2010.
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Shockley, Natalie. "Schizophrenia & information processing : a comparison of the prepulse inhibition, latent inhibition, P-50 gating, and mismatch negativity paradigms, with schizophrenia, bipolar and well control samples /." [St. Lucia, Qld.], 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17131.pdf.
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Postma, Peggy Margaret Ann. "An experimental and functional neuroimaging investigation into the effects of nicotine on prepulse inhibition of the startle reflex in schizophrenia." Thesis, City University London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269417.
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Shelton, Heath W. "The Effects of Two Novel Anti-Inflammatory Compounds On Prepulse Inhibition and Neural Microglia Cell Activation in a Rodent Model of Schizophrenia." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etd/3537.
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Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits and reduced microglia activation and thereby demonstrated the ability to treat both the behavioral and neuroinflammatory aspects of the disorder. These results are significant and suggest that neural TNFα is a potential pharmacological target for the treatment of schizophrenia.
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Bannbers, Elin. "The Effect of Steroid Hormones in the Female Brain During Different Reproductive States." Doctoral thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-175409.
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Women are twice as likely as men to suffer from depression and anxiety disorders and have an increased risk of onset during periods associated with hormonal changes, such as the postpartum period and the menopausal transition. Furthermore, some women seem more sensitive to normal hormone fluctuations across the menstrual cycle, since approximately 3-5% suffers from premenstrual dysphoric disorder (PMDD). Why these disorders are so common in women has not been established but there is a probable involvement of the ovarian hormones. The aim of this thesis was to investigate the effect of the ovarian hormones on the female brain during different reproductive states using psychological tests known to affect brain activity in different ways. Paper one examined the effect of the ovarian hormones on prepulse inhibition (PPI) on the acoustic startle response (ASR) and comprised cycling women and postmenopausal women. The cycling women had lower levels of PPI compared to postmenopausal women and postmenopausal women with moderate estradiol levels had lower PPI compared to postmenopausal women with low estradiol levels. Paper two examined the effect of anticipation and affective modulation on the ASR in women with PMDD and healthy controls. Women with PMDD have an increased modulation during anticipation of affective pictures compared to healthy controls during the luteal phase of the menstrual cycle. Paper three examined brain activity during response inhibition among women with PMDD and healthy controls by the use of a Go/NoGo task and fMRI. Women with PMDD displayed a decreased activity in the left insula during follicular phase and an increased activity during the luteal phase compared to controls. Paper four comprised women in the postpartum period and non-pregnant controls to examine brain activity during response inhibition. While this study revealed decreased activity at 4 weeks postpartum compared to 48 hours postpartum we cannot ascertain the role of the ovarian steroids, since none of the significant brain areas correlated with ovarian steroid or neurosteroid serum concentrations. The results of this thesis demonstrate that the ovarian hormones, or at least various hormonal states, have a probable impact on how the female brain works.
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Webber, Emily Sophia. "Fear and Assessment of Safety in Rats Selectively Bred for Differential Emission of 50 kHz Ultrasonic Vocalizations." Bowling Green State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1245687804.
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Lee, Jennifer Elizabeth. "Comparison of Auditory Thresholds Obtained with a Conditioned and an Unconditioned Response." University of Toledo / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1325738685.
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Day-Wilson, Katherine Mary. "Neuroanatomical studies of the isolation-reared rat with a deficit in prepulse inhibition of acoustic startle as a model for the sensorimotor gating deficits in schizophrenia." Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418807.
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Toua, Carl Christiaan. "Behavioural, pharmacological and neurochemical studies of social isolation rearing in rats / Carl Toua." Thesis, North-West University, 2007. http://hdl.handle.net/10394/1941.
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Annic, Agnès. "Physiopathologie des troubles de la sélectivité attentionnelle dans la maladie de Parkinson : rôle des processus de capture et de contrôle volontaire de l'attention." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S046/document.
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La maladie de Parkinson (MP) est la deuxième affection neurodégénérative la plus fréquente après la maladie d’Alzheimer. Elle se caractérise par un dysfonctionnement du système des ganglions de la base, en rapport avec une dégénérescence des neurones dopaminergiques de la substance noire compacte. A côté des symptômes moteurs, la MP s’accompagne de troubles cognitifs, en particulier une altération des capacités de sélectivité attentionnelle. Ce déficit attentionnel se traduit par des difficultés à sélectionner les informations pertinentes pour la conduite en cours et peut entraîner des troubles cognitifs légers. L’origine des troubles attentionnels reste imprécise : on ignore s'ils résultent d’une défaillance des mécanismes volontaires d’orientation de l’attention ou d'une perturbation des processus automatiques de capture attentionnelle. Le filtrage sensoriel permet de focaliser notre attention grâce à une sélection des informations pertinentes pour l’action en cours et une inhibition des informations non pertinentes. Il peut être exploré en neurophysiologie par le paradigme d’inhibition par le prepulse (PPI). Ce dernier correspond à l’atténuation de la réponse motrice et corticale suite à la présentation d’un stimulus sursautant (pulse) lorsque celui-ci est précédé de quelques millisecondes d’un stimulus non sursautant (prepulse). Le PPI est influencé par l’attention, son amplitude étant majorée lorsque l’attention est portée volontairement sur le prepulse. L’objectif général était donc de mieux identifier la nature des troubles de la sélectivité attentionnelle dans la MP par un paradigme actif de PPI au cours duquel la réponse corticale au pulse est enregistrée. Nous faisions l’hypothèse que les parkinsoniens présenteraient une inhibition plus faible que les témoins sains. En cas de défaillance de mobilisation volontaire des ressources attentionnelles, l'inhibition de la réponse corticale au pulse devrait être moins importante lorsque les ressources attentionnelles allouées au traitement du prepulse mettent en jeu la mobilisation volontaire de l’attention. A l’inverse, en cas de défaut de capture attentionnelle, l’inhibition de la réponse serait moins importante lorsque le traitement du prepulse implique les processus automatiques de capture.Pour répondre à cet objectif, nous avons dans un premier temps développé et validé un paradigme actif de PPI au cours duquel l’effet de la mobilisation volontaire de l’attention et de la capture attentionnelle sur le processus de filtrage sensoriel a été évalué. Pour ce faire, 26 témoins sains jeunes ont bénéficié d’un électroencéphalogramme à haute résolution tout en réalisant une tâche attentionnelle sur laquelle a été greffé un paradigme actif de PPI. Nous avons recueilli la réponse corticale évoquée et induite par la présentation du pulse. 16 témoins sains âgés, 16 patients parkinsoniens sans trouble cognitif et 16 patients avec troubles cognitifs légers ont bénéficié du même enregistrement au cours de la même tâche attentionnelle. Chez les témoins sains jeunes, nous avons montré que les processus de mobilisation volontaire de l’attention et de capture attentionnelle modulaient de façon différentielle la réponse évoquée et induite par la présentation du pulse. Au cours du vieillissement, nous avons observé une meilleure sensibilité de la réponse corticale induite, ce qui nous a conduit à choisir ce marqueur cortical pour évaluer le filtrage sensoriel dans la MP. Nos résultats montrent une réduction de l’inhibition de la réponse induite chez les parkinsoniens avec troubles cognitifs légers, confirmant la distractibilité. La MP s’accompagne aussi d’une altération dans la génération des oscillations corticales dans la bande de fréquence thêta quand la focalisation de l’attention est engagéeParkinson’s disease (PD) is the most frequent neurodegenerative disorder after Alzheimer’s disease. It is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta, causing a progressive loss of dopamine neurotransmission within the basal ganglia. Apart from motor symptoms, PD patients have cognitive disorders. Namely, focused attention is impaired and PD patients fail to select task-relevant information, leading sometimes to mild cognitive impairment (MCI). The origin of this impairment is still debated: PD-related selective attention deficit may be due either to a failure of goal-directed or stimulus-driven attention. Sensory gating helps the individuals to selectively allocate their attentional resources to salient stimuli and to inhibit irrelevant information. One of the physiological marker of this process is referred to as prepulse inhibition (PPI). It corresponds to the attenuation of the motor and cortical responses to a startling stimulus (pulse) when a non-startling stimulus (the prepulse) precedes the pulse by few milliseconds. PPI can be modulated by attention, its magnitude being greater after a to-be attended prepulse. Moreover, PPI is mediated by basal ganglia.The main aim of this work was to better identify the mechanisms involved in selective attention deficits in PD. We used an active PPI paradigm and recorded the cortical response to the pulse. We assumed that PD patients would exhibit a lower inhibition of the cortical response than healthy controls. If attention deficits in PD are related to an impairment of goal-directed attention, PD patients would exhibit lower inhibition after a to-be attended prepulse than in the other conditions. At the opposite, if it is due to a failure of stimulus-driven attention, inhibition would be lower after a prepulse which involuntarily captures attention than in the other conditions.In order to reach this objective, we have first developed and validated a new active PPI paradigm in order to investigate the role of goal-directed and stimulus-driven attention on sensory-cognitive gating. To this end, high resolution electroencephalogram was recorded in 26 young healthy subjects. They performed a selective attention task combined with an active PPI paradigm and the auditory-evoked and induced cortical response to the pulse was recorded. Then, the same procedure was administered in 16 elderly healthy subjects, 16 PD patients without MCI and 16 PD patients with MCI. In young healthy subjects, we found that stimulus-driven and goal-directed attention each had specific effects on the inhibition of the evoked and induced response to the pulse. The investigation of age-related changes on sensory gating revealed that the induced cortical response was more sensitive for assessing age-related changes than the evoked response. Then, we chose this cortical marker to investigate sensory gating in PD. Our results showed that PD patients with MCI exhibit lower inhibition of induced cortical response to the pulse than healthy controls. This finding confirms previous results showing a high distractibility in these patients. Moreover, PD patients exhibit impaired theta synchronization when focused attention was engaged
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Amador, Arjona Alejandro. "Role of NTRK3 in the extinction of fear memories and streess-coping: studies in a mouse model of panic disorder." Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7126.
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The correct development and function of CNS is critical for brain health of the organism. Early or chronic stress causes prominent alterations in brain function, and affects the expression of neurotrophic factors in limbic brain regions involved in the regulation of mood and cognition. Recent evidences have opened the idea that in complex organisms, an altered expression of certain neurotrophins by stress could be involved in the onset and pathophysiology of most psychiatric disorders, such as depression, squizophrenia or anxiety disorders. It is hypothesized that altered levels of neurotrophic factors could contribute to the atrophy and cell death of these regions, including the hippocampus and prefrontal cortex, which would produce a malfunction in limbic-related areas, and as a consequence, a precipitation or worsening of psychiatric illnesses. We were interested in panic disorder pathophysiology, which is a stress-related disorder and is characterized by an altered cognitive processing of emotional information. Although little evidence has been found supporting a neurotrophic role in PD, recent data has revealed that NT-3/TrkC signaling might play a key role in limbic system morphology and function. Therefore, we suggest that NT-3/TrkC system is involved in PD pathogenesis. The main objective in the work of this doctoral thesis lie to determine the role of NTRK3 gene, that codifies for TrKC, in emotional cognition and stress response processes that underlies PD. To this end, we used a genetically modified mouse model of NTRK3 overexpression, which was validated as a model of PD. Here, it is characterized the effects produced by the increase of NTRK3 expression in the CNS, focusing in neural alterations that might influence changes in cognitive processes involved in coping strategies. Moreover, it is studied the mechanisms that underlie in these processes by different approaches, 1/physiologically, measuring the HPA axis response, 2/brain activation, analyzing the activation pattern to a stress stimulus, 3/cellular and gene expression profiling, characterizing key brain regions in cognitive processes, and 4/pharmacologically, studying neurotransmitters function.
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Monte, Aline Santos. "Minociclina na prevenÃÃo e reversÃo dos sintomas tipo esquizofrenia induzidos por cetamina em camundongos: possÃvel envolvimento do estresse oxidativo e da via nitrÃrgica." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10909.
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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoA esquizofrenia à um transtorno mental grave que afeta cerca de 1 % da populaÃÃo acima da idade de 18 anos e à capaz de comprometer o pensamento, vontade prÃpria, percepÃÃo, afeto e interaÃÃo social. O efeito insuficiente da farmacoterapia atual sobre os sintomas negativos e dÃficits cognitivos reflete nossa mà compreensÃo da etiologia da esquizofrenia. Tem sido hipotetizado que as alteraÃÃes na sinalizaÃÃo nitrÃrgica e o desequilÃbrio oxidativo desempenham um papel na neurobiologia da esquizofrenia. EvidÃncias preliminares sugerem que o tratamento adjuvante com minociclina à eficaz para sintomas negativos e cognitivos desse transtorno. Assim, esse estudo investigou os efeitos da minociclina na prevenÃÃo e reversÃo de comportamentos tipo esquizofrenia induzidos por cetamina em camundongos. No protocolo de reversÃo, diferentes grupos de animais receberam cetamina (20 mg/kg) ou DMSO (veÃculo usado nos grupos controles) por 14 dias e, do 8 ao 14 dia, receberam adicionalmente minociclina (25 ou 50mg/kg), risperidona (0,5mg/kg) ou DMSO 30 minutos depois. No protocolo de prevenÃÃo, os camundongos foram prÃ-tratados com ambas as doses de minociclina, risperidona ou DMSO por 14 dias e, do 8 ao 14 dia, receberam adicionalmente cetamina 30 minutos depois. Todas as drogas foram administradas intraperitonealmente e uma vez ao dia. Comportamentos relacionados aos sintomas positivos (inibiÃÃo prÃ-pulso e atividade locomotora), negativos (interaÃÃo social) e cognitivos (labirinto Y) da esquizofrenia tambÃm foram avaliados. Glutationa (GSH), substÃncias reativas ao Ãcido tiobarbitÃrico (TBARS) e os nÃveis de nitrito foram medidos no cÃrtex prÃ-frontal (CPF), hipocampo (HC) e no corpo estriado (CE). Os resultados dos testes comportamentais mostraram que a cetamina promoveu um dÃficit no filtro sensÃrio-motor, aumento da atividade locomotora, diminuiÃÃo da interaÃÃo social e prejuÃzo na memÃria de trabalho. Praticamente todos esses parÃmetros foram prevenidos e revertidos pela administraÃÃo de minociclina (25 e 50mg/kg) e risperidona. A cetamina tambÃm promoveu alteraÃÃes nos marcadores oxidativos, atravÃs do aumento da peroxidaÃÃo lipÃdica e diminuiÃÃo dos nÃveis do antioxidante GSH, alÃm do aumento dos nÃveis de nitrito no CE. Seguindo a mesma linha dos resultados comportamentais, a minociclina e risperidona foram capazes de prevenir e reverter tais alteraÃÃes. Estes dados fornecem evidÃncias prÃ-clÃnicas para uma melhor avaliaÃÃo da minociclina como um novo agente antipsicÃtico e sugerem que seu mecanismo de aÃÃo inclui efeitos nos sistemas antioxidantes e nitrÃrgicos.
Schizophrenia is a serious mental disorder that affects approximately 1 % of the population over the age of 18 and is able to compromise the thought, will, perception, social interaction and affection. The insufficient effect of current pharmacotherapy on negative symptoms and cognitive deficits reflects our poor understanding of the etiology of schizophrenia. It has been hypothesized that oxidative imbalance and alterations in nitrergic signaling play a role in the neurobiology of schizophrenia. Preliminary evidence suggests that adjunctive minocycline treatment is efficacious for cognitive and negative symptoms of schizophrenia. Thus, this study investigated the effects of minocycline in the prevention and reversal of ketamine-induced schizophrenia-like behaviors in mice. In the reversal protocol, different groups of animals received ketamine (20 mg/kg) or DMSO (vehicle used in controls) for 14 days, and, from the 8th to 14th day, additionally received minocycline (25 or 50mg/kg), risperidone (0.5 mg / kg) or DMSO 30 minutes after. In the prevention protocol, mice were pre-treated with both doses of minocycline, risperidone or DMSO for 14 days, from the 8th to 14th day, additionally received ketamine 30 minutes later. All drugs were administered intraperitoneally and once a day. Behaviors related to positive (locomotor activity and prepulse inhibition of startle), negative (social interaction) and cognitive (Y maze) symptoms of schizophrenia were also assessed. Glutathione (GSH), thiobarbituric acid-reactive substances (TBARS) and nitrite levels were measured in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The result of behavioral tests showed that ketamine promoted a deficit in sensorimotor filter, increased locomotor activity, decreased social interaction and prejudice in working memory. Virtually all of these parameters were prevented and reversed by the administration of minocycline (25 and 50 mg/kg) and risperidone. Ketamine also promoted changes in oxidative markers by increasing lipid peroxidation and antioxidant GSH levels decrease, in addition to increased levels of nitrite in the ST. Following the same line of the behavioral results, minocycline and risperidone were able to prevent and reverse such changes.These data provide a rationale for evaluating minocycline as a novel psychotropic agent and suggest that its mechanism of action includes antioxidant and nitergic systems.
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Möller, Marisa. "Behavioural, neurochemical, inflammatory and mitichondrial markers following social isolation rearing in rats before and after selected deug intervention / Marisa Möller." Thesis, North-West University, 2012. http://hdl.handle.net/10394/9524.
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Purpose:
Schizophrenia is a progressive degenerative illness that has been causally linked to mitochondrial dysfunction, oxidative stress and a pro-inflammatory state. Social isolation rearing (SIR) in rats models the neurodevelopmental aspects of schizophrenia. The antioxidant and glutamate modulator, N-acetyl cysteine (NAC), has demonstrated therapeutic potential in schizophrenia as adjunctive treatment, although this has not been tested in the SIR model. The purpose of this study was to assess whether SIR induces changes in mitochondrial function (adenosine triphosphate (ATP)), pro- vs. anti-inflammatory cytokine balance, tryptophan metabolism, a disturbance in cortico-striatal monoamines and related metabolites, and associated alterations in behaviors akin to schizophrenia, viz. social interaction, object recognition memory and prepulse inhibition (PPI). Moreover, I evaluated whether these bio-behavioral alterations could be reversed with sub-chronic clozapine, or NAC, and whether NAC may bolster the response to clozapine treatment.
Methods: The objectives of the study were pursued through separately conducted studies. Male Sprague-Dawley (SD) rats (10 rats/group) were used in this study (Ethics number: NWU-0035-08-S5). Rats were randomly allocated to either social rearing or SIR for 8 weeks receiving either no treatment, vehicle, NAC (150 mg/kg/day), clozapine (5 mg/kg/day) or a combination of clozapine + NAC (CLZ + NAC) during the last 11 or 14 days of social rearing or SIR. After the 8 weeks, rats were tested for social interactive behaviors, object recognition memory and prepulse inhibition (PPI). Peripheral tryptophan metabolites (determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)) and pro- and anti-inflammatory cytokines (IL-4, IL-6, TNF-α, IFN-γ) (enzyme-linked immunosorbent assay (ELISA)) were determined. Cortico-striatal ATP (bioluminescence assay) and monoamines (high performance liquid chromatography (HPLC)) were also determined.
Results:
SIR-induced significant deficits in social interactive behaviours, object recognition memory and PPI, associated with increased peripheral kynurenine, quinolinic acid (QA), and pro-inflammatory cytokines, as well as a decrease in kynurenic acid (KYNA), neuroprotective ratio and anti-inflammatory cytokines. I also observed an increase in striatal, but reduced frontal cortical ATP, dopamine, serotonin as well as their metabolites and noradrenaline’s metabolite, with noradrenaline increased in both brain regions in SIR rats. A separate dose-response study of NAC (50, 150, 250 mg/kg/day) found 150 mg/kg to be the most appropriate dose for the NAC and CLZ + NAC studies. Clozapine, NAC as well as CLZ + NAC reversed all these changes, with NAC being less effective than CLZ alone. CLZ + NAC was found to be more effective than clozapine alone in reversing certain bio-behavioral alterations induced by SIR. In addition NAC alone dose dependently reversed most of the SIR induced alterations.
Conclusion:
SIR induces behavioral alterations, a pro-inflammatory state, mitochondrial dysfunction and cortico-striatal monoamine alterations, closely resembling evidence in schizophrenia. Importantly, all these bio-behavioral alterations were reversed with clozapine, NAC and CLZ + NAC treatment. However, CLZ + NAC was more effective than clozapine alone in reversing some bio-behavioral alterations, supporting the therapeutic application of NAC as adjunctive treatment in schizophrenia. In addition, NAC dose dependently reversed SIR-induced cortico-striatal serotonin, noradrenaline and metabolites, emphasizing NAC’s potential use in other anxiety and stress- related disorders.Thesis (PhD (Pharmacology))--North-West University, Potchefstroom Campus, 2013
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Longenecker, Ryan James. "Differential Pathologies Resulting From Sound Exposure: Tinnitus Vs. Hearing Loss." Kent State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1440684230.
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Vohra, Hiba Z. "Molecular Targets of Psychedelics and Their Role in Behavioral Models of Hallucinogenic Action." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/6012.
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Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in both rats and humans, attempts to translate this behavior to mice are rare. In contrast to prior gene knockout studies suggesting the mGluR2 is necessary for 5-HT2A agonist-induced HTR, mGluR2 knockout (Grm2-/-) mice still displayed HTR upon administration of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Additionally, DOI and lysergic acid diethylamide (LSD) produced unexpected improvements in PPI in male 126S6/Sv wild-type mice, depending on the experimental protocol used and the origin of the animals. Sex differences were observed as DOI-induced improvements in PPI were present in female 129S6/Sv mice of the same origin and tested with the same protocol as their male counterparts; this effect in females was absent in 5-HT2A knockout (Htr2a-/-) mice. The results of this study shed light on issues with replicability and reproducibility in science, the importance of highlighting the origin and background of animal subjects, and potential sex differences in hallucinogenic drug action.
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Meirsman, Aura Callia Carole. "Rôle du récepteur orphelin GPR88 dans les pathologies psychiatriques et motrices." Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ052/document.
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GPR88 est un récepteur couplé aux protéines G orphelin exprimé principalement au niveau du striatum spécifiquement dans les neurones moyens épineux de la voie striato-nigrale et de la voie striato-pallidale.Premièrement nous avons étudié les souris Gpr88 KO et montré des altérations biochimiques, structurales et comportementales. Aussi les résultats montrent que l’hyperactivité des souris Gpr88 KO est diminuée par l’administration de méthylphénidate. Deuxièmement nous avons montré que la diminution des comportements liés à l’anxiété dépend de GPR88 dans la voie striato-pallidale et que la coordination motrice est régulée par GPR88 dans le striatum adulte (injection AAV-Cre) et dans la voie striato-pallidale. Dernièrement, nous avons confirmé un déficit d’inhibition du prépulse chez les souris Gpr88 KO, mais aussi montré que celui-ci s’étend à la modalité visuelle et n’est pas lié à un déficit général d’inhibition ou à la délétion de Gpr88 dans les neurones striato-pallidauxAmong brain orphan G protein-coupled receptors, GPR88 shows high expression mainly in the striatum specifically in medium spiny neurons of both the striatonigral and striatopallidal pathwaysFirst, we examine full Gpr88 KO mice and show biochemical, structural and behavioral alterations. Results also show that the hyperactivity phenotype of Gpr88 KO mice is reversed by methylphenidate.Second, we show that Gpr88 in striatopallidal neurons (cKO approach) exerts anxiogénic activity and that motor coordination is regulated by GPR88 in the adult brain (AAV-Cre approach) and in the striatopallidal pathway.Finally, we confirmed previous data showing impaired acoustic prepulse inhibition in Gpr88 KO mice and further show that this deficit is not the result of a general inhibition deficit or of the lack of GPR88 in striatopallidal neurons
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Saber, Yasir Hazim. "Preclinical evaluation of a potential treatment for ADHD targeting the serotonin 1B receptor subtype." University of Toledo / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1566553528266516.
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Kask, Kristiina. "Hormones, Mood and Cognition." Doctoral thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9365.
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Ovarian steroid hormones are neuroactive steroids with widespread actions in the brain, and are thus able to influence mood, behavior and cognition. In this thesis the effects of progesterone withdrawal and the direct effects of the progesterone metabolite allopregnanolone are evaluated. Allopregnanolone, through binding to the GABAA receptor complex, enhances inhibitory neurotransmission, thus exerting anxiolytic, sedative and antiepileptic effects. The acoustic startle response (ASR) is a withdrawal reflex evoked by sudden or noxious auditory stimuli, and can be measured in humans as an eye blink. ASR is significantly increased in several anxiety disorders, and notably also during progesterone withdrawal. Sensorimotor gating can be assessed by measuring prepulse inhibition of the startle response (PPI). The CNS circuits regulating PPI are sensitive to hormone fluctuations. GABAergic drugs are involved in cognitive impairment and animal studies have indicated that allopregnanolone may inhibit learning. The main purpose of this research was to evaluate the behavioral effects of progesterone withdrawal on the startle response and sensorimotor gating in PMDD patients and healthy controls, in healthy third trimester pregnant women and healthy postpartum women. A second aim was to evaluate allopregnanolone effects on memory and cognition in healthy women and also on the startle response and PPI. We found that PMDD patients have an increased startle response across the menstrual cycle and a deficiency in sensorimotor gating during the late luteal phase. Ovarian steroids affect sensorimotor gating; pregnant women have lower levels of PPI than late postpartum women. Acutely administered allopregnanolone did not affect the ASR or PPI. Allopregnanolone impairs episodic memory in healthy women. In conclusion, our studies suggest that ovarian steroids, including allopregnanolone, do not influence the startle response. Ovarian steroids affect sensorimotor gating; pregnancy, a condition with high levels of ovarian steroids, suppresses PPI. Theoretically, the variability in PPI across reproductive events is due to effects mediated by the progesterone or estradiol receptors but is not mediated by allopregnanolone. PMDD patients display decreased PPI during the late luteal phase, suggesting underlying pathophysiology in common with other anxiety disorders. The most vulnerable memory system, the episodic memory, is impaired by the allopregnanolone in healthy women.
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Maple, Amanda Marie. "An Analysis of Nicotine Exacerbation of Reductions in PPI in a Rodent Model of Schizophrenia." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etd/2157.
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Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is known to be reduced when the dopamine D2 receptor is activated. We used a rodent model of psychosis in which increases in dopamine D2 receptor sensitivity are produced through neonatal quinpirole (a dopamine D2 / D3 agonist) treatment to rats. Rats were administered quinpirole (1mg/kg) or saline from postnatal day (P) 1-21. Rats were raised to adulthood and tested on PPI. Results showed that neonatal quinpirole treatment produced a significant reduction in PPI, and nicotine exacerbated this reduction. This reduction was partially blocked by the nicotinic antagonist mecamylamine. Brain tissue was analyzed for regulators of G-protein signaling (RGS) and results showed that neonatal quinpirole significantly decreased RGS9, but increased RGS17 as compared to controls. These results appear to indicate that the G-protein couples more efficiently to the D2 receptor, and nicotine exacerbates PPI deficits in D2 receptor-primed rats.
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Strauss, Laetitia. "Effects of chronic methamphetamine exposure during early or late phase development in normal and social isolation reared rats / Laetitia Strauss." Thesis, North-West University, 2012. http://hdl.handle.net/10394/9211.
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Methamphetamine (MA) abuse is a fast growing drug problem, and is the second most widely abused drug world-wide. MA abuse has been linked to the development of symptoms indistinguishable from schizophrenia, referred to as MA psychosis. MA abusing individuals, who most often comprise adolescents and young adults, are 11 times more likely than the general population to develop psychosis. Of further concern is that in utero exposure to MA is also a growing problem, with more women addicts choosing MA as their primary drug. This has significant implications for the neurodevelopment of the child, with subsequent behavioural deficits later in life. Epidemiological studies suggests that in utero or early life MA exposure places a vulnerable individual at greater risk for developing schizophrenia, although this has never been formerly studied either at clinical or pre-clinical level. Animal models of early life adversity, such as post-weaning social isolation rearing (SIR), can assist in understanding the underlying mechanisms in MA abuse and vulnerability to develop MA psychosis.
The aim of the current study was to investigate the long term effects of either prenatal (in utero) or early postnatal administration of MA on the development of schizophrenia-like behavioural and neurochemical abnormalities later in life.
In the in utero study, pregnant female Wistar rats received either saline (Sal) or MA 5 mg/kg/day for 16 days by subcutaneous (s.c.) injection , starting on prenatal day 13 (PreND-13) up to postnatal day 2 (PostND02). Male offspring were selected for the study. On PostND 21, the animals were weaned and reared under group or isolation reared conditions for 8 weeks. In the early postnatal study, adult male Wistar rats were divided into group reared and SIR conditions from PostND21. Either group received an escalating dose of MA twice a day (0.2 mg/kg – 6 mg/kg s.c.) or Sal for 16 days, from PostND35 to PostND50. Both in utero and early postnatal groups were then subjected to various behavioural tests on PostND78, including assessment of social interaction (SI) and prepulse inhibition (PPI) of acoustic startle. Following behavioural testing, rats were sacrificed and brains snap frozen for later analysis of cortico-striatal monoamine concentrations, superoxide dismutase activity and lipid peroxidation.
In the prenatally exposed group no differences in %PPI was observed, although group reared animals receiving MA and SIR animals receiving Sal or MA showed a decrease in social interactive behaviours, including approaching, time together and anogenital sniffing. SIR animals receiving Sal or MA also showed a decrease in rearing. Regarding self-directed behaviours, group reared animals receiving MA and SIR animals receiving Sal or MA showed an increase in self-grooming. Although some disturbances in regional brain monoamines were observed in the frontal cortex and striatum across the groups, this did not reach significance. A significant increase in malondialdehyde was observed in the striatum in group reared animals receiving MA as well as SIR animals receiving Sal or MA, indicating cell damage, possibly of redox origin.
In the early postnatal study, %PPI was significantly reduced in group reared animals receiving MA as well as in SIR animals receiving Sal or MA. Group reared animals receiving MA and SIR animals receiving Sal or MA showed a decrease in social interactive behaviours, including rearing, approaching, time together and anogenital sniffing. Regarding self-directed behaviours and locomotor activity, self-grooming and squares crossed was significantly increased in group reared animals receiving MA and SIR animals receiving Sal or MA. A significant increase in DA was evident in the frontal cortex of SIR and grouped housed animals receiving MA. DA in the MA + SIR combination was elevated but not significantly so. None of the treatments affected striatal monoamine levels. In the group reared animals receiving MA as well as the SIR animals receiving Sal or MA, a significant decrease in SOD activity was observed in the frontal cortex, indicating the presence of oxidative stress in this brain region. None of the parameters indicated an additive effect in MA + SIR treated animals.
In conclusion, prenatal exposure to MA led to some evidence of late-life behavioural and neurochemical abnormalities akin to schizophrenia, confirming its penchant for psychotogenic effects. However, chronic postnatal MA exposure was more emphatic, being as effective as SIR, a neurodevelopmental model of schizophrenia, in inducing deficits in the above-mentioned behavioural and neurochemical parameters. Thus, early adolescent abuse of MA is a significant risk factor for the later development of schizophrenia or psychosis. However, the risk appeared not to be exacerbated in a population at risk, i.e. in SIR animals.Thesis (MSc (Pharmacology))--North-West University, Potchefstroom Campus, 2013.
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"Comparative analgesic effects of prepulse inhibition and reduced voltage waveforms in defibrillation." THE GEORGE WASHINGTON UNIVERSITY, 2010. http://pqdtopen.proquest.com/#viewpdf?dispub=3397604.
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Faerman, Paul. "Pharmacological regulation of brain stem circuits mediating prepulse inhibition of startle in rats." 2004. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=81176&T=F.
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Wan, Yu-Yueh, and 萬雨樂. "The Effects of Social Isolation on Prepulse Inhibition Following Serotonin Depletion in Rats." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/58557809517022607962.
Full textAbstract:
碩士國防醫學院
生理學研究所
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Schizophrenia is a chronic major mental illness. Patients with schizophrenia exhibit the abnormalities in reality testing, cognitive function and emotional expression. In animal study, rats reared in social isolation following weanling would deprive their physical contact with others, and induce certain neurological and behavioral changes similar to those occur in schizophrenia. Sensorimotor gating deficit has been considered one of the major pathophysiology underlying schizophrenia, and possibly related to the symptoms such as auditory and visual hallucinations. The function of sensorimotor gating can be assessed by the test of acoustic startle response (ASR) and prepulse inhibition (PPI). The goal of the present study was to investigate the interactive effects of isolation rearing (IR) and central serotonergic function on PPI. In the present study, rats being social isolated for two months received a series of behavioral tests, including locomotor activity, elevated T maze (ETM), forced swim test (FST), and the PPI before and after the intervention of 5HT 1A activation following central lesion of serotonergic neurons. The lesion was executed by injection of neurotoxin 5,7-DHT (200 μg) into ICV. 8-OH-DPAT was given at the dose of 0, 10 and 100 ug (i.p.) ten days after the lesion. Animals were sacrificed after the behavioral tests and the expression of 5HT1A was evaluated by Western Blot method. The results revealed that IR rats had a higher locomotor activity in the novel environment; however, there were no significant difference between IR and social rats in the PPI. Further, in ETM experiment, IR rats exhibited a longer retaining time in the closed arm in the avoidance test, whereas no difference was found in the one-way escape test. In FST, no group difference was found in climbing, immobility and swimming. On the other hand, following the central 5HT depletion, both IR and social rats were found a decrease of 5HT level in the cortex、striatum、hippocampus、hypothalamus and thalamus, however in hypothalamus and thalamus IR unexpectedly had an increase of 5HT level. Moreover, as the 8-OH-DPAT was peripherally administered in rats with central 5HT lesion, the PPI performance had been found opposite according to the rearing conditions. While social rats exhibited an increase, IR rats exhibited a decrease of the PPI. The phenomenon can be also demonstrated in the expression of 5HT1A receptor in the amygdala in rats following 5HT depletion, while social rats had a reduced expression of 5HT1A receptor, IR rats oppositely had an elevated expression of 5HT1A receptor. The most important finding of the present study lied in that following central 5HT depletion, the role of 5HT1A receptor on the PPI performance appeared different between social and IR rats. The results possibly indicated that the abnormality of PPI induced by early-life stress might be relevant to the postsynaptic 5HT1A receptor.
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"Cellular Mechanisms Underlying the Effects of Repeated D2-like Agonist Treatment on Prepulse Inhibition." Doctoral diss., 2013. http://hdl.handle.net/2286/R.I.17790.
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abstract: Patients with schizophrenia have deficits in sensorimotor gating, the ability to gate out irrelevant stimuli in order to attend to relevant stimuli. Prepulse inhibition (PPI) of the startle response is a reliable and valid model of sensorimotor gating across species. Repeated D2-like agonist treatment alleviates prior PPI deficits in rats, termed a PPI recovery, and is observable 28 days after treatment. The aim of the current project is to illuminate the underlying mechanism for this persistent change of behavior and determine the clinical relevance of repeated D2-like agonist treatment. Our results revealed a significant increase in Delta FosB, a transcription factor, in the nucleus accumbens (NAc) 10 days after repeated D2-like agonist treatment. Additionally, we investigated if Delta FosB was necessary for long-lasting PPI recovery and discovered a bilateral infusion of dominant-negative Delta JunD prevented PPI recovery after repeated D2-like agonist treatment. To further develop the underlying mechanism of PPI recovery, we observed that dominant negative mutant cyclic adenosine monophosphate (cAMP) response biding element protein (CREB) prevented repeated D2-like agonist-induced Delta FosB expression in the NAc. We then compared our previous behavioral and intracellular findings to the results of repeated aripiprazole, a novel D2-like partial agonist antipsychotic, to determine if repeated D2-like receptor agonist action is a clinically relevant pharmacological approach. As compared to previous PPI recovery and Delta FosB expression after repeated D2-like agonist treatment, we found similar PPI recovery and Delta FosB expression after repeated aripiprazole treatment in rats. We can conclude that repeated D2-like agonist treatment produces persistent PPI recovery through CREB phosphorylation and Delta FosB, which is necessary for PPI recovery. Furthermore, this pharmacological approach produces behavioral and intracellular changes similar to an effective novel antipsychotic. These findings suggest the underlying intracellular mechanism for sustained PPI recovery is clinically relevant and may be a potential target of therapeutic intervention to alleviate sensorimotor gating deficits, which are associated with cognitive symptoms of schizophrenia.Dissertation/Thesis
Ph.D. Psychology 2013
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Chugani, Bindiya. "Parallels between Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls and the Role of Sensitization." Thesis, 2012. http://hdl.handle.net/1807/32235.
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Pathological gambling is a serious disorder with lifetime prevalence between 1.1-3.5%. Evidence suggests commonalities in the neurochemical basis of pathological gambling and psychostimulant addiction. However, parallel effects of gambling and a stimulant drug have not been assessed in the same subjects. This study employed a cross-priming strategy in which 12 male pathological gamblers and 11 male controls were exposed to a 15-minute slot machine game and d-amphetamine (0.4 mg/kg). Subjective, cognitive, electrophysiological, and physiological responses were assessed. Gamblers reported greater desire to gamble after both reinforcers, when baseline motivation was controlled. Conversely, gamblers exhibited diminished cardiovascular response to amphetamine. Gamblers also exhibited decreased pre-pulse inhibition (impaired sensorimotor gating), and deficits on this index predicted greater post-amphetamine desire to gamble and decreased heart rate response to the dose. Results are consistent with possible dopaminergic sensitization in pathological gamblers, but also suggest that central noradrenergic receptor deficits contribute importantly to these effects.
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IRA, Elisa. "EXTENDED ENDOPHENOTYPES IN EARLY PSYCHOSIS: IS THERE AN ASSOCIATION AMONG BRAIN STRUCTURES, NEUROLOGICAL SOFT SIGNS, NEUROPSYCHOLOGY, PREPULSE INHIBITION AND GENETICS?" Doctoral thesis, 2012. http://hdl.handle.net/11562/395538.
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BACKGROUND:
Gli Endofenotipi sono componenti stabili ed ereditabili dei disturbi psicotici, misurabili in laboratorio con metodi quantitativi di analisi. I marker di risonanza magnetica, i deficit neuropsicologici, la prepulse inhibition del riflesso di startle (PPI) e i neurological soft signs (NSS) sono alcuni tra gli endofenotipi più studiati per la schizofrenia. Un’evoluzione del concetto di endofenotipo è quella di “endofenotipo esteso” che definisce l'unione tra più endofenotipi funzionalmente associati tra loro.
OBIETTIVI:
Il presente progetto di Dottorato si pone lo scopo di:
1) condurre per la prima volta una revisione sistematica allo scopo di individuare potenziali "endofenotipi estesi", formati da deficit neuropsicologici e alterazioni cerebrali strutturali, associati al polimorfismo Val158Met del gene COMT;
2) testare per la prima volta, in una coorte di pazienti affetti da psicosi, l'ipotesi che i pazienti con alti livelli di NSS (sensory integration and sequencing of complex motor act), rilevati da una valutazione neurologica, hanno più elevati deficit di PPI e che i pazienti con elevati deficit di PPI e elevati livelli di NSS hanno maggiori sintomi negativi;
3) valutare per la prima volta, in una coorte di pazienti affetti da psicosi se i pazienti con il genotipo Val/Val del polimorfismo Val158Met del gene COMT hanno più elevati livelli di NSS (sensory integration and sequencing of complex motor act) e una minore prestazione nelle funzioni esecutive. E' stata inoltre valutata l'ipotesi di un'associazione tra elevati livelli di NSS e basse funzioni esecutive. Infine è stato ipotizzata un'associazione tra il genotipo Val/Val della COMT e contemporaneamente elevati livelli di NSS (sensory integration and sequencing of complex motor act) e basse prestazioni nelle funzioni cognitive.
METODI:
Per il primo obiettivo è stata condotta una revisione sistematica sui database Medline e PubMed per individuare i test neuropsicologici e le alterazioni cerebrali strutturali legati al polimorfimso Val158Met del gene COMT e per verificare se gli endofenotipi cerebrali strutturali e neuropsicologici individuati sono associati tra loro. Infine sono stati proposti alcuni "endofenotipi estesi".
Per il secondo obiettivo è stata reclutata una coorte di pazienti psicotici in contatto con il Servizio di Salute Mentale di Verona Sud (Italia) ed è stata sottoposta alle valutazioni della PPI e dei NSS. Inoltre è stato reclutato un gruppo di controllo.
Per il terzo obiettivo, è stata reclutata una coorte di pazienti affetti da psicosi, che hanno donato il loro DNA e sono stati sottoposti alla valutazione dei NSS e a una valutazione neuropsicologica. I dati sono stati raccolti nell'ambito di tre studi epidemiologici multicentrici, condotti rispettivamente in Veneto (Italia) e a Londra Sud, Nottingham e Bristol (Regno Unito): il "Psychosis Incident Cohort Outcome Study" (PICOS), l'"Aetiology and Ethnicity in Schizophrenia and Other Psychoses study (AESOP) " and il "Genetics and Psychotic Illness study (GAP)". Inoltre è stata inclusa una coorte di pazienti psicotici in contatto con il Servizio di Salute Mentale di Verona Sud, Italia.
RISULTATI:
Rispetto al primo obiettivo, sono stati proposti tre "endofenotipi estesi" associati al polimorfismo Val158Met del gene COMT; un endofenotipo caratterizzato da: 1) la performance all'N-back e il volume della corteccia prefrontale, 2) la performance all'N-back e il volume del lobo mediale temporale, 3) la performance al CPT e il volume della corteccia prefrontale.
Rispetto al secondo obiettivo, sono stati sottoposti alle valutazioni della PPI e dei NSS quindici pazienti affetti da psicosi con una durata di malattia uguale o inferiore a cinque anni e quindici soggetti di controllo. I risultati hanno dimostrato che nei pazienti non erano evidenziabili maggiori livelli di deficit di PPI ma solo più elevati livelli di NSS (p<0.01), rispetto ai soggetti controllo. Più elevati livelli di NSS non erano associati a deficit di PPI. I deficit di PPI non erano correlati con nessuna caratteristica clinica; al contrario i NSS sensory integration signs erano correlati positivamente ai sintomi negativi (p<0,01).
Rispetto al terzo obiettivo, sono stati inclusi nel nostro studio quattrocentonovantotto pazienti affetti da psicosi. I risultati hanno evidenziato che il genotipo Met/Met era associato ad alti livelli di NSS sequencing of complex motor acts (p=0,034) e a basse prestazioni nelle funzioni esecutive (p<0,01) nei soggetti Caucasici ma non negli Africani e Afro-caraibici. I pazienti Caucasici con NSS sequencing of complex motor acts più elevati dimostravano anche peggiori funzioni esecutive (p<0,05). Tra i pazienti Caucasici che presentavano sia alti livelli di NSS sequencing of complex motor acts sia basse funzioni esecutive è stata riscontrata una più elevata percentuale del genotipo Met/Met, mentre il genotipo Val/Val era maggiormente presente nei pazienti che presentavano sia bassi livelli di NSS sequencing of complex motor acts sia alte funzioni cognitive e il genotipo Val/Met era più frequenti tra i pazienti che presentavano o alti livelli di NSS sequencing of complex o basse funzioni esecutive (Chi quadrato p=0,016).
CONCLUSIONI:
Concludendo, lo scopo di questo progetto è quello di contribuire a chiarire i potenziali meccanismi sottostanti l'esordio della psicosi, al fine di migliorare l'assessment e contribuire a definire nuove strategie di prevenzione e migliori trattamenti per tale disturbo.BACKGROUND: Endophenotypes are defined as heritable and stable components of the psychotic disorder, with the advantage of being measurable with quantitative methods and amenable to laboratory assessment. Examples of currently investigated endophenotypes in schizophrenia are neuroimaging markers, neuropsychological deficit, prepulse inhibition of the startle reflex (PPI), and neurological soft signs (NSS). In multigenerational families with schizophrenia, a co-segregation between some endophenotypes, such as magnetic resonance imaging (MRI) and neuropsychological measures, has been found. Moving from this observation, some authors have recently introduced the concept of “extended endophenotype”, referring to the proposal of combining multiple endophenotypes functionally associated with each other. AIMS: The present PhD project aims at: 1) performing for the first time a systematic review of the potential role of neuropsychological impairments and brain structural abnormalities in relation to the COMT Val158Met polymorphism as potential “extended endophenotypes” in psychosis; 2) testing for the first time, in a cohort of patients with psychosis that patients with higher levels of NSS sensory integration and NSS motor sequencing signs elicited by a neurological evaluation show higher PPI deficits and that patients with PPI deficits and high NSS scores have high level of negative symptoms. 3) investigating for the first time, in cohort of patients with psychosis, that patients with the Val/Val genotype of the COMT Val158Met polymorphism have higher score of NSS (sensory integration and sequencing of complex motor acts) and lower executive function. The hypothesis of an association between high NSS and lower executive function was also tested. Moreover, we hypothesized that the COMT Val/Val genotype would be associated with both higher NSS (sensory integration and sequencing of complex motor acts) and poorer executive function. METHODS: For the Aim 1, we searched the PubMed and Medline databases to systematically identify the neuropsychological tasks and brain structural variations related to COMT Val158Met across psychosis spectrum disorders and to verify if the neuropsychological and the brain structural endophenotypes identified were associated with each other. Finally we propose some "extended endophenotypes". For the Aim 2 a cohort of psychotic patients in contact with the South Verona Community-based Mental Health Service (CMHS), Italy, during a period of three years, was recruited and underwent PPI and NSS evaluations. Moreover a group of matched healthy controls was recruited. For the Aim 3, 4 cohort of subjects with psychosis were recruited, gave their DNA, underwent NSS and neuropsychological evaluation. The data were collected within the framework of three multisite epidemiological studies of first episode psychosis, conducted respectively in Veneto (Italy) and South London, Nottingham and Bristol (UK): the Psychosis Incident Cohort Outcome Study (PICOS), the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study and the Genetics and Psychotic Illness study (GAP). Moreover a cohort of psychotic patients in contact with the South Verona Community-based Mental Health Service (CMHS), Italy, was included. RESULTS: Regarding the 1st aim, three proposals of extended endophenotypes associated with COMT Val158Met polymorphism were identified; an extended endophenotype characterised by: 1) N-back performance and prefrontal cortex volumes, 2) N-back performance and medial temporal lobe volumes and 3) CPT performance, prefrontal volumes. Regarding the 2nd aim fifteen subjects affected by psychosis with a duration of illness equal or less than 5 years and fifteen healthy controls underwent PPI and NSS evaluations. Results showed that the patients did not exhibit higher levels of PPI deficits but only higher levels of NSS (p<0.01), as compared to healthy controls. Higher NSS rates were not associated with PPI deficits. PPI deficits did not correlate with any clinical characteristic; inversely, NSS sensory integration signs correlated positively with negative symptoms (p<0.01). Regarding the 3rd aim, four hundred ninety eight patients with psychosis were included in our study. We found that the Met/Met genotype is associated with higher sequencing of complex motor acts signs (p=0,034) and with lower executive function (p<0,01) in Caucasian but not in African and African-Caribbean individuals. Patients with higher sequencing of complex motor acts signs exhibited also lower executive function in Caucasians (p<0,05). Caucasian patients with both higher sequencing of complex motor acts signs and poorer executive function showed an higher percentage of Met/Met genotype, whereas the percentage of Val/Val individuals was higher in patients with both lower sequencing of complex motor acts signs and higher executive function and the Val/Met genotype was more frequent among patients with either higher sequencing of complex motor acts signs or poorer executive function (Chi Square, p=0,016). CONCLUSION: In conclusion, the purpose of this project is to contribute to clarifying the potential mechanisms underlying the onset of psychosis, in order to improve the assessment of the illness and to contribute to defining new prevention strategies and better treatment interventions for psychosis.
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Joshi, Namrata. "Adolescent environmental challenges affect adult function in male and female Long Evans rats." 2014. http://hdl.handle.net/10222/50415.
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Stress in adolescence is a putative risk factor for developing mental illnesses such as schizophrenia and mood disorders. Symptoms for these illnesses first emerge in late adolescence and early adulthood, with both incidence and severity being sexually dimorphic. Animal models can shed light on the neurobiological underpinnings of these disorders by allowing one to explore the relationship between a risk factor such as stress, and development of symptoms. In the current work the role of adolescent stress is explored in the development of biomarkers that are associated with adolescent-onset illnesses using Long Evans rats. Repeated exposure to predator odour was combined with social isolation during adolescence to create a novel stressor model. The specific objectives of this study were to determine (i) if repeated predator odour exposure altered measures related to sensorimotor gating (measured as prepulse inhibition, PPI), startle, and emotionality, and (ii) whether social support affected the outcome of predator odour stress. Predator odour elicited immediate avoidance, which did not habituate with repeated exposures, suggesting a strong behavioural stress response. In contrast to past work, few significant long-term effects were observed in animals exposed to predator odour compared with ones exposed to a non-threatening odour. Unexpectedly, animals exposed to a no odour (control) condition displayed altered PPI, startle response, anxiety-related behaviour, and memory, compared to rats exposed to a non-threatening, control odour or a predator odour. Moreover, the no odour animals showed altered expression of dopamine D2R receptor protein in the medial prefrontal cortex. The outcomes for this group were remarkably similar to those seen in animals raised in social isolation, suggesting an underlying similarity in the neurobiological mechanisms associated with these experiences that likely can be traced to being raised in environments lacking adequate social and physical complexity. Sex differences were noted in PPI, startle response, tests of anxiety- and depression-like behaviour, memory, and levels of dopamine D2R receptors, although the sex of the animal did not interact with stressor treatment to affect these measures. In conclusion, results of the current work provide further evidence for the importance of the social and physical environment to normal development during adolescence, as well as the importance of being male versus female.
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Zhuang, Alex. "The role of GABA-B in sensorigating processing disorders in rat models, an autoradiographic study." Thesis, 2019. https://hdl.handle.net/2144/37070.
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INTRODUCTION: The process of sensorimotor gating is a neurological phenomenon referring to the brain’s ability to process and filter out stimuli in order to prevent an overflow of information. This phenomenon can be operationally measured by prepulse inhibition, which is the attenuation of a stimulus-induced startle response by introducing a milder preceding stimulus. Studies have shown that impairment of prepulse inhibition (PPI) has been correlated with diseases such as schizophrenia and autism spectrum disorder. Many brain areas, including the superior colliculus (SC), inferior colliculus (IC), mediodorsal thalamus (MD), basolateral amygdala (BLA), anterior cingulate cortex (ACC), and ventral hippocampus (VHPC), have been implicated in playing important roles in prepulse inhibition. While many studies have implicated GABA-A receptors in playing a role in PPI regulation, little work has been done on GABA-B receptors. An established rat model with induced prepulse inhibition impairment was used in this study. PPI impairment was induced via injection of the glutamate receptor antagonist dizocilpine. A subgroup of rats was also treated with the antihistamine pyrilamine to reverse the effects of dizocilpine.
OBJECTIVES: The aims of this study are to: 1. Expand the understanding of prepulse inhibition in the context of neurological and developmental diseases such as autism spectrum disorder (ASD) and schizophrenia; 2. Identify potential significant differences within GABA-B receptor densities in the rat SC, IC, MD, BLA, ACC, or VHPC between treatment groups with and without dizocilpine and groups with and without pyrilamine.
METHODS: Histological brain slides harvested from 36 Sprague-Dawley rats were provided by Dr. Edward Levin from Duke University’s Neurobehavioral Research Lab for this study. The brain slides were incubated in a radioligand solution specific for GABA-B receptors and exposed to autoradiograph film for approximately 12 weeks. The films were developed in a dark room and scanned electronically. GABA-B receptor densities were measured from the images and the data was analyzed using ANOVA and independent T tests.
RESULTS: ANOVA testing revealed significant differences between treatment groups in the MD and VHPC. However, only the MD was found to have significant GABA-B receptor differences when comparing the dizocilpine and pyrilamine treatment groups to the control group. The VHPC was found to have significant differences in GABA-B receptor densities when directly comparing the dizocilpine group to the pyrilamine treatment group, rather than to the control group. There were no significant differences in GABA-B receptor densities as a result of either dizocilpine or pyrilamine treatment in the SC, IC, BLA, ACC, or VHPC.
CONCLUSION: Changes in GABA-B receptor levels appear to play a role in both the impairment and rescue of PPI in the rat MD. It does not appear to play a role in the SC, IC, BLA, ACC, or VHPC for either the impairment or rescue of PPI function.
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Glawatz, Christiane Heidrun Ulrike [Verfasser]. "Untersuchungen zum Einfluß von Persönlichkeitsfaktoren gesunder Menschen auf die Prepulse-Inhibition des akustischen Schreckreflexes / vorgelegt von Christiane Heidrun Ulrike Glawatz." 2005. http://d-nb.info/976065169/34.
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COZZUTO, GIUSEPPE. "Differenze individuali nei sistemi di attivazione e inibizione comportamentale nella risposta di “startle” e nell’inibizione della risposta motoria." Doctoral thesis, 2011. http://hdl.handle.net/11573/917199.
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Il lavoro di tesi esamina in maniera approfondita i meccanismi di elaborazione dell’informazione studiando sia le prime fasi di selezione e processamento dell’ informazioni in entrata (sensorimotor gating) che della conseguente emissione di una risposta motoria o della sua inibizione, in relazione i tratti temperamentali. Tale indagine ha previsto lo studio dei correlati neurali e dei segnali bioelettrici delle risposte. Nella prima ricerca viene approfondita la relazione tra il sistemi di approccio (BAS), di inibizione (BIS) e di attacco/fuga (FFFS), postulati dalla teoria di J. Gray, e la modulazione della risposta di startle mediante l’utilizzo del paradigma di Prepulse Inhibition. Particolare attenzione è stata data allo studio della relazione tra questa risposta e il sistema difensivo modulato dalle dimensioni temperamentali dell’ansia e della paura. Nella seconda ricerca i suddetti sistemi comportamentali vengono messi in relazione questa volta all’abilità di inibire una risposta motoria precedentemente programma mediante l’utilizzo di un compito di Stop-Signal con compenso monetario. Inoltre è stata valutata l’influenza che tratti temperamentali quali l’impulsività e l’ansia possono avere sulle capacità di inibizione. A completamento di entrambi gli studi l’utilizzo del software sLORETA, per la localizzazione dei generatori neurali delle componenti dei potenziali evento-correlati, ha permesso un confronto con quelle ricerche che hanno approfondito lo studio dei substrati neurali dei meccanismi di sensorimotor gating. I risultati hanno evidenziato come alcuni stili comportamentali possano influenzare disfunzionalmente i processi di gating sensorio e motorio. In conclusione, sia la risposta di startle che il compito di Stop-Signal, producendo indici comportamentali manifesti potrebbero quindi rivelarsi degli ottimi strumenti per valutare fattori predisponenti e precipitanti nell’insorgere di condizioni patologiche, affiancati alla comune diagnostica psicometrica.
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Poggi, Giulia. "Unraveling psychiatric sub-phenotypes: The price of the reduction of myelin basic protein." Doctoral thesis, 2016. http://hdl.handle.net/11858/00-1735-0000-0028-87E0-B.
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