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1
De, La Fuente Barrigon C. « Dopamine and serotonin metabolism in Parkinsonian models ». Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10054116/.
Texte intégralRésumé :
Parkinson’s disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra. Different pathogenic mechanisms have been implicated, including loss of mitochondrial complex I function and dysfunction of lysosomal glucocerebrosidase (GBA1) (Neumann et al., 2009; Schapira et al., 1990). Also, it has been hypothesised that serotonin metabolism could be affected in these patients due to the number of enzymes shared by both pathways (Albizu et al., 2011). This thesis considers the potential involvement of complex I and GBA1 in PD using HPLC analysis of changes in the extracellular levels of the metabolites of dopamine and serotonin, and the expression and activity of the enzymes of the dopamine pathway. Using SH-SY5Y cells, complex I deficiency was modelled using rotenone, and GBA1 deficiency was modelled using conduritol B epoxide (CBE). Inhibition of mitochondrial complex I or GBA1 significantly increased extracellular concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), direct products of the degradation by monoamine oxidase (MAO) of dopamine and serotonin respectively. These results suggest increased MAO activity, providing evidence for the involvement of impaired complex I or GBA1 activity in the dopamine deficiency seen in PD. As MAO produces hydrogen peroxide as a side-product, its increased activity could enhance the oxidative stress present in PD (Dias et al., 2013). Therefore, intracellular GSH levels were quantified to determine whether the antioxidant mechanisms were affected, but no changes were observed. In addition to the main project, I collaborated with a number of groups to study monoamine metabolism in parkinsonian models. Also, the glycoprofile of cerebrospinal fluid (CSF) of patients with and without impaired dopamine metabolism was studied to explore the possibility of using glycans as pathologic biomarkers.
2
Manrique, Muñante Rubén. « Love : there is (bio)chemistry between us ». Revista de Química, 2014. http://repositorio.pucp.edu.pe/index/handle/123456789/99292.
Texte intégralRésumé :
El enamoramiento implica procesos bioquímicos en los que sustancias como neurotransmisores, neuromoduladores y hormonas interaccionan con células nerviosas u otros órganos. Al estar enamorados, los niveles de dopamina aumentan generando atención, deseo y motivación en todo lo relacionado al ser amado. La serotonina, por el contrario, se presenta en concentraciones bajas en este estado. La oxitocina, por su parte, entra en juego cuando la demanda de dopamina no se logra suplir y es crucial al entablar relaciones de largo plazo. El entendimiento del mecanismo de la oxitocina en el ser humano es crucial no solo para el conocimiento académico sino también porque brinda luces para el tratamiento de algunos desórdenes psicológicos.Romantic love involves biochemical processes in which substances such as neurotransmitters, neuromodulators and hormones interact with other nerve cells or organs. When being in love, dopamine levels increases, generating attention, desire and motivation in everything related to the beloved person. Serotonin, however, is present in low levels in this state. When the body does not supply the necessary amount of dopamine, oxytocin is released. Oxytocin is vital in long term relationships. Understanding the mechanism of oxytocin in humans is crucial not only for academic knowledge of the chemistry of love but also because it provides new lights for the treatment of some psychological disorders.
3
Burke, Mark 1975. « Factors that influence the dopamine neuron as revealed by dopamine transporter expression ». Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85892.
Texte intégralRésumé :
The primary focus of the present thesis is the exploration of factors that influence the dopamine (DA) neuron by examining the expression of the dopamine transporter (DAT), a marker of the DA neuron. The secondary focus of this thesis is on the serotonin neuron and in particular the serotonin transporter (SERT), a marker of the serotonin neuron. To this end three distinct and separate models have been employed. The goals of this thesis were: (1) to test the hypothesis that monoamine oxidase inhibition during development alters serotonergic innervation in the cortex and raphe, while not affecting relative DA innervation of nigrostriatal pathway, (2) to test the hypothesis that elevated brain levels of hypoxanthine (Hx) deleteriously affect the DA neuron, and (3) to test the hypothesis that densities of DAT and SERT in brainstem cell body regions distinguish alcohol-preferring vervet monkeys with different behavioral patterns of ethanol consumption.Alterations in the activity of monoamine oxidase (MAO), a degradative enzyme that plays an important role in regulating levels of monoamine transmitters, may have a profound effect on brain development. The present study investigates relative DA and serotonin innervation of cortical and subcortical areas, measured by DAT and SERT densities, following MAO inhibition (A or B or A+B) in mice throughout gestation and early post-natal development. DAT binding was unaltered within the nigrostriatal pathway. The most significant finding reported here is that the combined MAO-A+B inhibition significantly reduced SERT binding by 25% in both the cortex and raphe nucleus. Lower levels of SERT binding were apparent during the early post-natal period (PND 14), a period during which pups were still exposed to MAO inhibitors in the dam's milk, but also persisted into later life (PND's 35 and 90) after inhibitors were no longer being administered. Persistent effects were restricted to cortex and raphe, suggesting a relative vulnerability of these regions to alterations in monoamine transmitter levels during development.
The second study presents data demonstrating that Hx delivered intracerebroventricularly significantly reduces the number of tyrosine hydroxylase immunoreactive cells (TH-ir) in the substantia nigra by 22% and 30%, at 7 and 21 days, respectively. After 3 days of Hx administration, striatal DA and serotonin were elevated over control levels by 22% and 25%, respectively, but returned to control levels by 7 days. The serotonin metabolite 5-HIAA was elevated after 3 days of Hx, but levels of DA metabolites were not different from control. Locomotion, a behavior thought to be related to DA transmission, was elevated following Hx treatment, as were presynaptic markers of the DA system such as DAT and TH protein levels. The persistent reduction in TH positive cell numbers suggests that Hx damages or kills DA neurons. The increase in intracellular DA at early time points suggests that Hx might interfere with DA release, possibly by temporarily inactivating DA neurons. These findings are consistent with the hypothesis that Hx, a purine significantly elevated in blood and CSF of Lesch-Nyhan patients, maybe involved in DA dysfunction.
Studies on alcohol abuse have focused on the mesolimbic DA pathway and the serotonergic influence within this pathway. Here we report that abstinent binge-drinking monkeys have significant reductions of SERT binding, and to a lesser extent, DAT binding in the midbrain region, while abstinent heavy-drinking subjects have elevated levels of DAT binding, as compared to controls. Both mesolimbic and nigrostriatal pathways are affected. CSF levels of both HVA and 5-HIAA substantiate the neuroanatomical differences between binge- and heavy-drinking vervets. Taken together, these findings provide a neurochemical profile with which to further distinguish subtypes of alcohol-preferring vervet monkeys.
4
Dassanayake, Ashlea Fiona. « Dual dopamine/serotonin treatment approach for addictive behaviour ». Thesis, University of Canterbury. Department of Psychology, 2013. http://hdl.handle.net/10092/7945.
Texte intégralRésumé :
Illicit drug abuse and addiction is a major problem in New Zealand and worldwide with approximately 12% of illicit drug users classified as having drug dependence or drug-use disorders. The chronically relapsing nature of drug addiction is a prominent feature of this disorder and a significant barrier to treating addiction. Amphetamine-type drugs, more than any other class of drugs, have seen an increase in global usage since the early 1990's. The lack of approved medications for the treatment of stimulant addiction together with an increasing treatment demand drives the need for pharmaceutical intervention. Substitute treatment approaches primarily focus on the dopamine (DA) system. However, several lines of research implicate a dual role for serotonin (5-HT). Using a benztropine (BZT) analogue, JHW 007 (JHW), and an atypical antidepressant, trazodone (TRAZ), we sought to test whether the combined modulation of DA and 5-HT during a period of extinction produced greater attenuation to drug-induced reinstatement compared to either DA or 5-HT alone. One hundred and two (102) male Long Evans rats were tested using an extinction-reinstatement model of methamphetamine (MA) addiction in conditioned place preference (CPP) (n=72) and self-administration (n=30) experimental designs. We hypothesised that a combined DA/5-HT treatment would further attenuate MA-induced reinstatement. Findings showed that JHW significantly attenuated MA-induced reinstatement in our self-administration model but not CPP, while TRAZ failed to significantly attenuate reinstatement in both experiments. The combination treatment group showed a mild attenuation to drug seeking with CPP, but this finding was not significant. Due to time restrictions, we did not test the combination group using a self-administration procedure. Unfortunately we were unable to fully address our initially proposed hypothesis, but our results with JHW add further support to this BZT analogue as a promising stimulant abuse medication.
5
Teles, Rita Tique Arriaga. « Efeito do treino na neurobioquímica cerebral do cão ». Master's thesis, Universidade de Évora, 2018. http://hdl.handle.net/10174/23173.
Texte intégralRésumé :
Com o objetivo de perceber de se o treino afeta a comunicação química do cérebro canino de uma forma permanente, estudaram-se dois grupos de cães: um grupo de cães treinado com marcadores e outro grupo sem contacto com nenhum tipo de treino. Foram recolhidas amostras sanguíneas dos dois grupos e medidas as concentrações de serotonina e dopamina. Os valores médios encontrados para a serotonina e dopamina para o grupo de controlo foram de 269.66 μg/l 56,97 ng/l respetivamente. Para a serotonina, a comparação das médias revelou diferenças entre os grupos (p=0,087), havendo uma diminuição no grupo de cães treinados. Já a dopamina não se verificou ser diferente entres os dois grupos estudados (p=0,2). As vias dopaminérgicas ativadas em situações de compulsão/adição são as mesmas que se ativam no circuito do reforço. Também os valores de serotonina estão diminuídos nesses casos, sugerindo que poderá haver uma componente compulsiva/aditiva em cães treinados; ABSTRACT:
The effect of training markers in the cerebral neurochemistry of the dog
To understand if dog training affects permanently the chemical communication of canine brain, two groups of dogs were studied: one group had dogs trained with markers and the other one had dogs without any type of training. Blood samples were collected from both groups and concentrations of serotonin and dopamine were measured. The mean values found for serotonin and dopamine for the control group were 269.66 μg/l and 56.93 ng/l respectively. Comparison of means of the groups revealed different values of serotonin between the two groups (p-value= 0,087) having a decrease in serotonin in the trained dog group. As for dopamine, it was not found to be different between the two groups studied (p-value=0,2). The dopaminergic pathways activated in compulsion/addition situations are the same ones that activate in the reinforcement circuit. Also, serotonin levels are decreased in these cases, suggesting that there may be a compulsive/additive component in trained dogs.
6
Garcila-Argulello, Segundo Francisco. « Development of dopamine and serotonin agonist radioligands for PET studies ». Thesis, Imperial College London, 2007. http://hdl.handle.net/10044/1/8377.
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Servidio, Susan. « Serotonergic modulation of a dopaminergic \"model\" of parkinsonism in the rat : neurochemical and clinical considerations / ». The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487260859496757.
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Chernoloz, Olga. « Reciprocal Interactions Between Monoamines as a Basis for the Antidepressant Response Potential ». Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/22663.
Texte intégralRésumé :
Despite substantial progress in the area of depression research, the current treatments for Major Depressive Disorder (MDD) remain suboptimal. Therefore, various medications are often used as augmenting agents in pharmacotherapy of treatment-resistant MDD. Despite the relative clinical success, little is known about the precise mechanisms of their antidepressant action.
The present work was focused on describing the effects of three drugs with distinctive pharmacological properties (pramipexole, aripiprazole, and quetiapine) on function of the monoaminergic systems involved in the pathophysiology and treatment of MDD. Reciprocal interactions between the monoamines serotonin, norepinephrine, and dopamine systems allow the drugs targeting one neuronal entity to modify the function of the other two chemospecific entities.
Electrophysiological experiments were carried out in anaesthetized rats after 2 and 14 days of drug administration to determine their immediate and the clinically-relevant long-term effects upon monoaminergic systems.
Pramipexole is a selective D2-like agonist with no affinity for any other types of receptors. It is currently approved for use in Parkinson’s disorder and the restless leg syndrome. Long-term pramipexole administration resulted in a net increase in function of both dopamine and serotonin systems.
Aripiprazole is a unique antipsychotic medication. Unlike all other representatives of this pharmacological class that antagonize D2 receptor, this drug acts as a partial agonist at this site. Chronic administration of aripiprazole elevated the discharge rate of the serotonin neurons, presumably increasing the overall serotonergic neurotransmission.
Like aripiprazole, quetiapine is one of three atypical antypsicotic drugs approved for use in MDD. Prolonged administration of quetiapine led to a significant increase in both noradrenergic and serotonergic neurotransmission. Importantly, the clinically counter-productive decrease in the spontaneous firing of catecholaminergic neurons, induced by SSRIs, was overturned by the concomitant administration of both aripiprazole and quetiapine.
The increase in serotonergic neurotransmission was a consistent finding between all three drugs studied herein. In every case this enhancement was attained in a distinctive manner. Understanding of the precise mechanisms leading to the amplification/normalization of function of monoamines enables potential construction of optimal treatment strategies thereby allowing clinicians greater pharmacological flexibility in the management of depressive symptoms.
9
Herman, Anna. « Alteration of Monoaminergic Neuronal Firing by Acute Administration of Cariprazine : An In Vivo Electrophysiological Study ». Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36713.
Texte intégralRésumé :
Cariprazine is a novel dopamine (DA) and serotonin (5-HT) partial agonist
with an in vitro receptor affinity profile that endows it with the potential to be used
successfully in the treatment of both unipolar and bipolar disorders. The objective
of this study was to determine whether in vitro findings with cariprazine lead to
functional alterations of monoamine systems in the intact rat brain. In vivo
electrophysiological recordings were carried out in male Sprague-Dawley rats
under chloral hydrate anesthesia. Dorsal raphé nucleus (DRN), locus coeruleus
(LC), and hippocampus cornu ammonis region 3 (CA3) pyramidal neurons were
recorded and cariprazine was administered systemically by intravenous injection
or locally through iontophoresis. In the DRN, cariprazine induced a complete
inhibition of the firing of 5-HT neurons, which was fully reversed by the selective
5-HT1A antagonist WAY100.635. In the LC, the inhibitory effect of the preferential
5-HT2A agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) was reversed by
cariprazine with an ED50 value of 67 µg/kg, i.v., and it did not block the inhibitory
effect of the α2-adrenergic agonist clonidine. In the hippocampus, when
cariprazine was administered by iontophoresis, it inhibited the firing of pyramidal
neurons, but it did not dampen the suppressant effect of 5-HT. These results
indicate that, in vivo, cariprazine acts as a 5-HT1A agonist in the DRN, as an
antagonist on 5-HT2A receptors controlling the firing of NE neurons, and is a full
agonist at 5-HT1A receptors located on pyramidal neurons of the hippocampus.
The modulatory actions of cariprazine on the 5-HT and NE systems may
contribute to its reported effectiveness in depressive episodes.
10
Gill, Mark D. « Aminergic modulation of spontaneous and reflexly generated motor output of crayfish walking leg motor neurons ». Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262842.
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Raghanti, Mary Ann. « Differences in cortical dopamine, acetylcholine, and serotonin innervation among humans, chimpanzees, and macaques ». [Kent, Ohio] : Kent State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=kent1168280662.
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Grimm, Stefanie Heidrun. « Development of MS binding assays addressing the human dopamine, norepinephrine, and serotonin transporter ». Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-183766.
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Andersson, Daniel. « Dopamine and the regulation of movements : significance of nigral and striatal dopamine release in normal, hemiparkinsonian and dyskinetic rats / ». Göteborg : Dept. of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, 2009. http://hdl.handle.net/2077/19327.
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Sobik, Laura Elizabeth. « Sibling-based association study of dopamine transporter, serotonin transporter, and dopamine-4 receptor polymorphisms and disordered eating behavior in young adults ». Connect to online resource, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3288863.
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Agnoli, Laura. « Modulation of cortical cognitive funtions by dopamine and serotonin receptors in the dorsal striatum ». Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533126.
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Bengtson, Colin Peter. « Serotonin and dopamine actions on basal forebrain neurons in the ventral pallidum in vitro / ». [St. Lucia, Qld.], 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16862.pdf.
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Troppmann, Britta. « Klonierung und Charakterisierung aminerger Rezeptoren der Amerikanischen Schabe Periplaneta americana ». Phd thesis, Universität Potsdam, 2009. http://opus.kobv.de/ubp/volltexte/2009/3661/.
Texte intégralRésumé :
Biogene Amine sind kleine organische Verbindungen, die sowohl bei Vertebraten als auch bei Invertebraten als Neurotransmitter, Neuromodulatoren und/oder Neurohormone wirken. Sie bilden eine bedeutende Gruppe von Botenstoffen und entfalten ihre Wirkungen vornehmlich über die Bindung an G-Protein-gekoppelte Rezeptoren.
Bei Insekten wurde eine Vielzahl von Wirkungen biogener Amine beschrieben. Das führte schon frühzeitig zur Vermutung, dass Insekten (u. a. Invertebraten) wie die Wirbeltiere ein diverses Repertoire an aminergen Rezeptoren besitzen. Für ein umfassendes Verständnis der komplexen physiologischen Wirkungen biogener Amine fehlten jedoch wichtige Informationen über die molekulare Identität der entsprechenden Rezeptorproteine und ihrer pharmakologischen Eigenschaften, ihre Lokalisation und ihre intrazellulären Reaktionspartner. Viele bei Schaben gut untersuchte (neuro)physiologische Prozesse sowie Verhaltensweisen werden durch Serotonin und Dopamin gesteuert bzw. moduliert. Über die beteiligten Rezeptoren ist jedoch bisher vergleichsweise wenig bekannt. Die Klonierung und Charakterisierung von Serotonin- und Dopaminrezeptoren der Amerikanischen Schabe P. americana ist damit ein längst überfälliger Schritt auf dem Weg zu einem umfassenden Verständnis der vielfältigen Wirkungen biogener Amine bei Insekten.
Durch die Anwendung verschiedener Klonierungsstrategien konnten cDNAs isoliert werden, die für potentielle Serotoninrezeptoren und einen Dopaminrezeptor kodieren. Die Sequenzen weisen die größte Ähnlichkeit zu Mitgliedern der 5-HT1- und 5-HT7-Rezeptorklassen bzw. den Invertebratentyp-Dopaminrezeptoren auf. Die isolierten Rezeptoren der Amerikanischen Schabe wurden dementsprechend Pea(Periplaneta americana)5-HT1, Pea5-HT7 und PeaDop2 benannt. Das Hydropathieprofil dieser Rezeptoren postuliert das Vorhandensein der charakteristischen heptahelikalen Architektur G-Protein-gekoppelter Rezeptoren. Die abgeleiteten Aminosäuresequenzen zeigen typische Merkmale aminerger Rezeptoren. So sind Aminosäuren, die bedeutend für die Ligandenbindung, die Rezeptoraktivierung und die Kopplung an GProteine sind, in den Rezeptoren konserviert.
Expressionsstudien zeigten eine auffallend hohe Expression aller drei Rezeptor-mRNAs im Gehirn sowie in den Speicheldrüsen. Im Rahmen dieser Arbeit wurden polyklonale Antikörper gegen den Pea5-HT1-Rezeptor sowie den PeaDop2-Rezeptor hergestellt. Der anti-Pea5-HT1-Antikörper detektiert im Homogenat von Schabengehirnen, Speicheldrüsen und Pea5-HT1-exprimierenden HEK 293-Zellen die glykosylierte Form des Rezeptors. In Gehirnschnitten markiert der anti-Pea5-HT1-Antikörper spezifisch einige Zellkörper in der Pars intercerebralis und deren Axone, welche in den Corpora cardiaca Nerv I projizieren. Der PeaDop2-Rezeptor wurde durch den spezifischen anti-PeaDop2-Antikörper in Neuronen mit Somata im anterioren Randbereich der Medulla nachgewiesen. Diese Neurone innervieren die optischen Loben und projizieren in das ventrolaterale Protocerebrum.
Die intrazellulären Signalwege der heterolog exprimierten Pea5-HT1- und PeaDop2-Rezeptoren wurden in HEK 293-Zellen untersucht. Die Aktivierung des Pea5-HT1-Rezeptors durch Serotonin führt zur Hemmung der cAMP-Synthese. Des Weiteren wurde gezeigt, dass der Rezeptor konstitutive Aktivität besitzt. WAY 100635, ein hoch selektiver 5-HT1A-Rezeptorantagonist, wurde als wirksamer inverser Agonist am Pea5-HT1-Rezeptor identifiziert. Der stabil exprimierte PeaDop2-Rezeptor antwortet auf eine Aktivierung durch Dopamin mit einer Erhöhung der cAMP-Konzentration. Eine C-terminal trunkierte Variante dieses Rezeptors ist eigenständig nicht funktional.
Die Ergebnisse der vorliegenden Arbeit indizieren, dass die untersuchten aminergen Rezeptoren im zentralen Nervensystems der Schabe an der Informationsverarbeitung beteiligt sind und verschiedene physiologische Prozesse in peripheren Organen regulieren. Mit der Klonierung und funktionellen Charakterisierung der ersten Serotoninrezeptoren und eines Dopaminrezeptors ist damit eine wichtige Grundlage für die Untersuchung ihrer Funktionen geschaffen worden.Biogenic amines are small organic compounds that act as neurotransmitters, neuromodulators and/or neurohormones in vertebrates and in invertebrates. They form an important group of messenger substances and mediate their diverse effects primarily by binding to G protein-coupled receptors. The molecular identification as well as the functional and pharmacological characterization of these receptors is crucial for the comprehension of the intracellular signaling pathways activated by biogenic amines. This work describes the molecular and functional characterization of the first serotonin receptors and an invertebrate-type dopamine receptor of the American cockroach, Periplaneta americana. Using a PCR-strategy based on degenerate primers and RACE-PCR three cDNAs encoding for putative biogenic amine receptors were isolated from P. americana brain cDNA (Pea5-ht1, Pea5-ht7, Peadop2). The deduced amino acid sequences display major characteristics common to all G protein-coupled receptors. Primarily Distribution of receptor mRNA was investigated by RT-PCR. The analysis revealed a high mRNA expression level for all three receptors in the brain and salivary glands. The distribution of the Pea5HT1 and PeaDop2 receptor proteins was analyzed by immunohistochemistry with specific affinity-purified polyclonal antibodies. Both receptor proteins are expressed in brain and salivary glands. Furthermore the cellular distribution of the receptors was investigated by immunocytochemistry on brain sections. The anti-Pea5-HT1 receptor antibody specifically labelled some large somata in the pars intercerebralis. Labeled axons of these neurons pass down the anterior surface of the brain and cross over in the chiasma region of the corpora cardiaca nerve 1. The PeaDop2 receptor was detected in neurons with somata at the anterior edge of the medulla bilaterally innervating the optic lobes and projecting to the ventro-lateral protocerebrum. In order to clarify the functional and pharmacological properties of the cloned receptors, we studied HEK 293 cell lines stably expressing Pea5-HT1 or PeaDop2. Activation of Pea5-HT1 expressing cells by serotonin reduced adenylyl cyclase activity in a dose-dependent manner. The Pea5-HT1 receptor was expressed as a constitutively active receptor with methiothepin acting as a neutral antagonist and WAY 100635 as an inverse agonist. The activation of the PeaDop2 receptor by dopamine induced an increase in intracellular cAMP level, whereas a C-terminally truncated splice variant of this receptor does not exhibit any functional property by itself. The results of this work suggest important roles of the investigated receptors in various areas of the cockroach brain. The molecular and pharmacological characterization of the first serotonin receptors and a dopamine receptor of the cockroach now provides the basis for forthcoming studies regarding the significance of these particular receptors for cockroach behavior and physiology
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Ozaki, Norio. « Pharmacogenetics of antipsychoatics ». Nagoya University School of Medicine, 2004. http://hdl.handle.net/2237/5398.
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Clark, Merry C. « Monoaminergic receptors in the stomatogastric nervous system characterization and localization in Panulirus interruptus / ». unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-04212008-151237/.
Texte intégralRésumé :
Thesis (Ph. D.)--Georgia State University, 2008.Title from file title page. Deborah Baro, committee chair; Paul Katz, Charles Derby, Susanna Greer, Teryl Frey, committee members. Electronic text (249 p. : col. ill.) : digital, PDF file. Description based on contents viewed August 8, 2008. Includes bibliographical references (p. 222-249).
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Kaur, Harneet. « Synthesis And Evaluation Of Novel Tropane Compounds As Potential Therapeutics For Drug Abuse ». ScholarWorks@UNO, 2007. http://scholarworks.uno.edu/td/586.
Texte intégralRésumé :
In an effort to search for potential therapeutic agents for cocaine addiction, a novel class of compounds was synthesized and evaluated for in vitro dopamine and serotonin transporter affinities. These unique 3ƒÀ-aryl-3ƒ¿-arylmethoxytropane analogues incorporated the structure of dopamine selective 2-substituted-3-phenyltropanes and the design of serotonin selective meperidine derivatives. In general, the 3ƒÀ-aryl-3ƒ¿-arylmethoxytropane analogues exhibited greater potency for the serotonin transporter than the dopamine transporter. The most potent compounds of this series were 3ƒÀ-phenyl-3ƒ¿.(3, 4-dichlorophenyl)methoxy-8.azabicyclo [3.2.1]nortropane (Ki = 0.06 nM) and 3ƒÀ-(4Œ-chlorophenyl)-3ƒ¿.(4-chlorophenyl)methoxy-8. azabicyclo[3.2.1]nortropane (Ki = 0.09 nM) at the serotonin transporter and their binding affinities were equipotent with paroxetine and fluoxetine (Prozac). A series of 8-azabicyclo[3.2.1]oct-2-ene derivatives were synthesized from 3-tropinone based on the structure of triple re-uptake inhibitor, DOV 216, 303. The compounds were designed as potential triple re-uptake inhibitors which could exhibit equipotent affinities at the monoamine transporters for dopamine, serotonin and norepinephrine. A short and efficient synthetic methodology was developed for the synthesis of unique compounds which could exhibit potency for both the dopamine and serotonin transporters. The 3ƒÀ-aryl-3ƒ¿-(4Œ, 4-disubstituteddiphenylmethoxy)tropane analogues were designed as hybrid structures of the dopamine transporter selective benztropines and the serotonin transporter selective meperidine derivatives.
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Bortolotto, Vandreza Cardoso. « Crisina reverte o comportamento tipo depressivo e as alterações monoaminérgicas induzidas pelo hipotireoidismo em camundongos fêmeas ». Universidade Federal do Pampa, 2017. http://dspace.unipampa.edu.br:8080/jspui/handle/riu/3372.
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A glândula tireoide é uma das maiores glândulas do corpo, responsável pela produção de triiodotironina (T3) e tiroxina (T4), hormônios responsáveis pela homeostase do organismo. A redução na produção destes hormônios leva a um quadro de hipotireoidismo. O hipotireoidismo é uma desordem endócrina, mais prevalente no sexo feminino, e que pode causar uma série de alterações comportamentais e neurológicas, dentre elas a depressão. O flavonoide crisina, presente no maracujá do mato, própolis e mel de abelha, vem sendo estudado a alguns anos, sendo relatados seus efeitos antioxidantes, anticancerígenos, antihiperglicêmicos, ansiolíticos, e atualmente tem-se demonstrado sua atividade antidepressiva. O objetivo deste estudo foi investigar a ação terapêutica da crisina em modelo tipo depressivo induzido pelo hipotireoidismo em camundongos fêmeas C57BL/6 adultas. Primeiramernte os animais foram divididos em dois grandes grupos (n=20): controle e hipotireoidismo. O hipotireoidismo foi induzido por exposição contínua ao fármaco antitireoideo metimazol (MTZ) 0,1% + 0,475% de sucralose, durante 31 dias na água. No 31º dia foi retirado sangue da veia caudal e determinado os níveis de T3 e T4. Após os animais foram separados em quatro grupos (n=10): controle, hipotireoidismo, crisina, hipotireoidismo + crisina. A crisina (20mg/kg) foi administrada diariamente por 28 dias, via oral. Ao final do tratamento, os animais passaram por testes comportamentais de campo aberto (TCA), nado forçado (TNF) e suspensão de cauda (TSC), após realizou-se eutanásia nos animais, e coletou-se o sangue por punção cardíaca para análise bioquímica de T3 e T4, e retirou-se as estruturas cerebrais hipocampo e córtex pré frontal, para análises neuroquímicas de serotonina (5-HT), dopamina (DA), norepinefrina (NA). Nossos resultados demonstraram que os animais com hipotireoidismo apresentaram um aumento no tempo de imobilidade nos testes de TNF e TSC e a crisina foi capaz de reverter este tempo em ambos os testes. Demonstrou-se também que a crisina foi capaz de restaurar os níveis de neurotransmissores: 5-HT em ambas estruturas cerebrais e DA no hipocampo dos animais com hipotireoidismo, corroborando com os resultados dos testes comportamentais, nos quais o TNF está relacionado com o sistema serotoninérgico e o TSC com o sistema dopaminérgico. Em conclusão, nossos resultados demonstram pela primeira vez que a crisina é capaz de reverter o estado tipo depressivo induzido pelo hipotireoidismo, possivelmente por normalizar os níveis de 5-HT e DA.
The thyroid gland is one of the largest glands in the body, it produces triiodothyronine (T3) and thyroxine (T4), these hormones are responsible for body homeostasis. The reduction in the production of these hormones leads to hypothyroidism. The hypothyroidism is an endocrine disorder, more prevalent in females, which can cause a number of behavioral and neurological changes, including depression. The chrysin flavonoid present in the passion fruit of the bush, propolis and bee honey, has been studied for some years, being reported your antioxidant effect, anticancer, antihyperglycemic, anxiolytic, and currently your antidepressant activity was demonstrated. The objective of this study was to investigate the therapeutic action of chrysin in a model of like-depression induced by hypothyroidism in adult C57BL/6 female mice. First, the animals were divided into two groups (n=20): control and hypothyroidism. Hypothyroidism was induced by continuous exposure to the antithyroid drug methimazole (MTZ) 0.1% + 0.475% sucralose for 31 days on water. On the 31st day blood was drawn from the caudal vein and T3 and T4 levels were determined. After the animals were separated into four groups (n=10): control, hypothyroidism, chrysin, hypothyroidism + chrysin. The treatment of chrysin (20mg/kg) was administered daily for 28 days, orally. At the end of treatment the animals they passed for behavioral tests of open field test (OFT), forced swimming test (FST) and tail suspension test (TST), performed euthanasia in the animals, and collected the blood by cardiac puncture for biochemical analyze of T3 and T4, and the hippocampus and prefrontal cortex brain structures were removed for neurochemical analyzes of serotonin (5-HT), dopamine (DA), norepinephrine (NA). Our results demonstrated that animals with hypothyroidism showed an increase in the time of immobility in the tests of FST and TST and the chrysin was able to reverse this time in both tests. It was also demonstrated that the chrysin was able to restore the levels of neurotransmitters: 5-HT in both structures cerebral and DA in the hippocampus of animals with hypothyroidism, corroborating with the results of behavioral tests, in which FST is related to the serotonergic system and the TST with the dopaminergic system. In conclusion, our results demonstrate for the first time that chrysin is able of reversing the depressive-induced state induced by hypothyroidism, possibly by normalizing 5-HT and DA levels.
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Thompson, Miles. « Mutation screening of dopamine and serotonin candidate genes in Tourette's syndrome and alcohol-dependent patients ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29330.pdf.
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Clark, Martin. « An electrophysiological investigation of the extrinsic modulation of ventral pallidum neurons by dopamine and serotonin ». Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22438/.
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The ventral pallidum (VP) is a key output structure of the basal ganglia and has multiple connections with cortical and limbic regions. The VP is modulated by extrinsic neurotransmitters, including dopamine and serotonin, but the cellular mechanisms underlying this modulation are only partially understood. This thesis describes an in vitro electrophysiological investigation of such extrinsic modulation employing extracellular multi electrode recordings of the VP and pharmacological manipulations. Our data provide novel information on how dopamine modulates VP neurons acting both pre- and post-synaptically. Presynaptic excitatory effects of dopamine are mediated by D1-like and D2-like receptors, through effects on glutamate release and subsequently ionotropic and metabotropic glutamate receptor activation. Postsynaptic, direct effects are mediated by D2-like receptors and induce decreases in firing frequency within the VP. Our data identifies two populations of neurons in the VP, which can be consistently separated by their spike half-width profile and their responses to D2-like receptor agonists. With regard to serotonin, both excitatory and inhibitory responses to its application were observed in the VP. Our data suggests that excitatory effects of Serotonin (5HT) are presynaptic, while the inhibitory responses to 5HT are postsynaptic, direct effects. Our data also suggest that 5HT1a, 5HT5A and 5HT7 receptors are responsible for increases in firing frequency to 5HT application and 5-HT2c receptors are likely candidates for the decrease in firing frequency to 5HT application in the VP. We also investigated the effects of electric activation of NAc inputs to the VP. Our data are consistent with the literature, showing that NAc inputs inhibit VP neurons. Overall, these results cast light on the cellular mechanism by which dopamine and serotonin modulate VP neurons and have important implications for our understanding of the role the VP plays in reward processing and related dysfunctions.
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Alex, Katherine D. « 5-HT2C SEROTONIN RECEPTORS : CELLULAR LOCALIZATION AND CONTROL OF DOPAMINERGIC PATHWAYS IN THE RAT BRAIN ». Connect to text online, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1164766901.
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Orejarena, Maria Juliana. « Neurobiological mechanisms involved in MDMA-Seeking behaviour and relapse ». Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7229.
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(+) 3,4-metilendioximetanfetamina (MDMA), popularmente conocida como "éxtasis", es una droga susceptible de producir adicción en algunos individuos. Actualmente es consumida principalmente por adolescentes y jóvenes. Los particulares efectos psicoactivos inducidos por la MDMA, permiten distinguirlo de manera clara de otros psicoestimulantes o compuestos alucinógenos. Esta droga actúa principalmente activando el sistema dopaminérgico y serotonérgico en los circuitos neurales de placer. Sin embargo, los mecanismos neurobiológicos implicados en las propiedades adictivas de esta droga no han sido aún esclarecidos. El trabajo presentado en esta Tesis Doctoral ha puesto de manifiesto algunos aspectos claves de estos procesos que eran desconocidos hasta el momento. Hemos encontrado que el receptor de serotonina 5-HT 2A participa de forma critica en las propiedades reforzantes de la MDMA, contrario a lo observado en el caso de otros psicoestimulantes. Además, el bloqueo farmacológico de este receptor puede prevenir la reinstauración de la búsqueda de la MDMA, desencadenada por un estímulo o clave previamente asociado a su consumo. Estos efectos pueden ser debidos al bloqueo del control excitatorio que normalmente ejercen estos receptores sobre los niveles de dopamina en estructuras mesolímbicas, como ha sido revelado en nuestros estudios de microdiálisis. Hemos demostrado también que la MDMA puede actuar como clave interoceptiva y desencadenar la recaída a la búsqueda y consumo de cocaína. Adicionalmente, nuestros estudios han mostrado que tanto la activación del sistema dopaminérgico mesolímbico, como los cambios en la expresión génica en diferentes ´areas cerebrales que ocurren tras la administración de la MDMA, dependen de si el sujeto participa de manera activa en el consumo de esta droga, o si por el contrario la recibe de forma pasiva. En conclusión, este trabajo resalta la importancia de los procesos de aprendizaje y memoria sobre las propiedades reforzantes/recompensantes de la MDMA. Además, nuestras investigaciones aportan nuevas evidencias en relación a la participación del sistema serotonérgico en la búsqueda y recaída al consumo de esta droga.(+) 3,4-methylenedioxymethamphetamine (MDMA), commonly known as "ecstasy", is currently a highly consumed drug with liability to produce addiction in some individuals. MDMA induces unique psychoactive effects that clearly distinguish it from hallucinogenic or psychostimulant drugs. MDMA mainly enhances the activity of both the serotonergic and the dopaminergic system in the esolimbic brain reward pathways. However, the neurobiological mechanisms underlying its possible addictive properties are still not fully understood. In the present work, we have contributed to this subject by establishing that the serotonin 5-HT2A receptor, in contrast to what has been observed for other drugs of abuse, is critical for MDMA-induced reinforcement. Moreover, the pharmacological blockade of this receptor can prevent cue-induced relapse. This effect is possibly mediated by its excitatory control over basal and MDMA-induced increase in midbrain dopamine, as supported by our microdialysis data. Furthermore, we have also shown that MDMA can act as an interoceptive cue to induce relapse to cocaine-seeking behaviour. Additionally, we demonstrated differential changes at the level of the dopaminergic brain reward pathway and gene expression changes in different brain areas, following self-administeredMDMAin comparison to passive administration. These results underpin the impact of a learning component in the rewarding/reinforcing properties of MDMA, and provide new evidence for the serotonergic involvement in MDMA-seeking behavior and relapse.
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Scheiner, Ricarda, Arnd Baumann et Wolfgang Blenau. « Aminergic control and modulation of honeybee behaviour ». Universität Potsdam, 2006. http://opus.kobv.de/ubp/texte_eingeschraenkt_verlag/2010/4610/.
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Biogenic amines are important messenger substances in the central nervous system and in peripheral organs of vertebrates and of invertebrates. The honeybee, Apis mellifera, is excellently suited to uncover the functions of biogenic amines in behaviour, because it has an extensive behavioural repertoire, with a number of biogenic amine receptors characterised in this insect. In the honeybee, the biogenic amines dopamine, octopamine, serotonin and tyramine modulate neuronal functions in various ways. Dopamine and serotonin are present in high concentrations in the bee brain, whereas octopamine and tyramine are less abundant. Octopamine is a key molecule for the control of honeybee behaviour. It generally has an arousing effect and leads to higher sensitivity for sensory inputs, better learning performance and increased foraging behaviour. Tyramine has been suggested to act antagonistically to octopamine, but only few experimental data are available for this amine. Dopamine and serotonin often have antagonistic or inhibitory effects as compared to octopamine. Biogenic amines bind to membrane receptors that primarily belong to the large gene-family of GTP-binding (G) protein coupled receptors. Receptor activation leads to transient changes in concentrations of intracellular second messengers such as cAMP, IP3 and/or Ca2+. Although several biogenic amine receptors from the honeybee have been cloned and characterised more recently, many genes still remain to be identified. The availability of the completely sequenced genome of Apis mellifera will contribute substantially to closing this gap. In this review, we will discuss the present knowledge on how biogenic amines and their receptor-mediated cellular responses modulate different behaviours of honeybees including learning processes and division of labour.
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Ghanbari, Ramez. « Impact of Medications Used in the Treatment of Mood Disorders on Monoaminergic Systems ». Thesis, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/19829.
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While selective serotonin (5-HT) reuptake inhibitors (SSRIs) are utilized as the first-line strategy in treating depression, new approaches are still desired. Using in vivo electrophysiological techniques, the effects of co-administration of bupropion with the SSRI escitalopram on the firing rate of dorsal raphe 5-HT and locus coeruleus norepinephrine (NE) neurons were investigated. Escitalopram significantly decreased the firing of 5-HT and NE neurons at day 2. The 5-HT firing rate, unlike that of NE, recovered after the 14-day escitalopram regimen. Bupropion did not increase 5-HT firing but decreased that of NE after 2 days. Following 14-day bupropion, 5-HT firing was markedly enhanced, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited after 2, but partially recovered after 14 days.
Although sustained bupropion administration did not alter the sensitivity of 5-HT1A receptors in hippocampus, the tonic activation of postsynaptic 5-HT1A receptors was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats. The function of terminal 5-HT1B autoreceptors was not changed. The inhibitory action of α2-adrenergic receptors on 5-HT terminals was, however, diminished. The function of terminal α2-adrenergic autoreceptors was also attenuated in rats given bupropion for 14 days.
Administration of the antidepressant trazodone suppressed the 5-HT firing at day 2, which recovered to baseline following 14 days. Prolonged trazodone-administration enhanced the tonic activation of postsynaptic 5-HT1A receptors in hippocampus, and decreased the function of terminal 5-HT1B autoreceptors.
Finally, a novel psychotropic agent asenapine showed potent antagonistic activity at 5-HT2A, D2, and α2-adrenoceptors. Asenapine, however, acted as a partial agonist at 5-HT1A receptors in dorsal raphe and hippocampus.
Overall, the therapeutic effects of various antidepressants may be, at least in part, due to the enhancement of 5-HT and/or NE neurotransmission.
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Garriock, Holly Ann. « Genetics of Major Depressive Disorder in Treatment Resistance and Tryptophan Depletion ». Diss., Tucson, Arizona : University of Arizona, 2006. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1462%5F1%5Fm.pdf&type=application/pdf.
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Cararas, Shaine A. « Synthesis and Biological Evaluation of Novel GBR 12909 Tropane and Azetidine Hybrid Analogues ». ScholarWorks@UNO, 2007. http://scholarworks.uno.edu/td/565.
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The high affinity, selective dopamine transporter ligand GBR 12909 has served as a template for the design of two novel classes of dopamine transporter ligands. A series of 3-[2- (diarylmethoxyethyidenyl)]-N-substituted tropane derivatives were synthesized and the binding affinities of these compounds were determined at the dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in rat brain tissue preparations. The tropane derivatives were found to exhibit more potent affinity and selectivity for DAT than GBR 12909. From the SAR of the tropane analogues and GBR 12909, a novel series of 3-[2-(diarylmethoxyethylidenyl)]-Nsubstituted azetidine derivatives has been developed.
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Mysiak, Karolina Sandra. « The role of monoamines in the development and regeneration of the zebrafish spinal cord ». Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25855.
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The hallmark of an adult mammalian central nervous system is the inability to regenerate after an injury. Zebrafish, on the other hand, have an astounding regenerative capacity. After a spinal cord lesion, zebrafish can re-establish the damaged neuronal network and regain their swimming ability within weeks. This is partly due to the presence of the ependymal radial glia (ERGs), which line the wall of the central canal and act as the stem/progenitor cells of the spinal cord. Under homeostatic conditions the ERGs are largely quiescent, however, the lesion triggers them to proliferate and replace cells that have been lost due to the damage. Previous studies have shown that the regeneration of the motor neurons is affected by the signalling pathways similar to those governing the first development of these cells during embryogenesis, such as Sonic hedgehog, Notch and dopamine signalling. Serotonin (5-HT), similar to dopamine, is a monoaminergic neurotransmitter with a wide range of physiological and behavioural functions. It has also been shown to play a role during development of the nervous system. In this doctoral thesis I address the hypothesis that 5-HT has a positive effect on the development and adult regeneration of motor neurons. In addition, I expand on the previously discovered augmenting effect of dopamine on motor neuron development, by analysing the downstream pathways of its action. I show that during the development, incubating embryos in 5-HT increases the proliferation of the motor neuron progenitor (pMN) cells, which leads to augmented motor neuron production. RT-PCR on FAC sorted pMN cells highlights a number of serotonergic receptors that might be responsible for this effect. Although the downstream pathways are still unknown, 5-HT appears not to act on the sonic hedgehog canonical pathway, as shown by the unchanged expression of the hedgehog effector gene, patched2 after 5-HT treatment. I show that 5-HT does not affect the generation of vsx1+ or pax2a+ interneurons, suggesting that it has a predominant effect on motor neuron production. In the intact spinal cord of an adult zebrafish, the pMN-like ERGs express serotonergic receptors, indicating they are responsive to 5-HT stimulation. After a lesion, 5-HT administration enhances the proliferation of the pMN-like ERGs caudal to the lesion site resulting in an increase in the number of newborn motor neurons. Rostral to the lesion site, administration of exogenous 5-HT does not have an effect on the ERG proliferation, possibly due to the fact that the endogenous source of 5-HT, in the form of the descending axons, is still present and might already elicit a maximal response of the progenitor cells. 5-HT does not have an effect on the proliferation of the progenitor cells dorsal or ventral to the pMNlike domain, nor does it affect the regeneration of the serotonergic interneurons. These results suggest that 5-HT from the brain preferentially contributes to the regeneration of the motor neurons. Dopamine is another monoamine shown to enhance motor neuron production during the development and regeneration. To investigate the downstream pathways of dopamine signalling on motor neuron production during embryogenesis, RNA-sequencing was performed on FAC sorted pMN cells after a treatment with a dopamine agonist, pergolide. The results yielded 14 differentially expressed genes (FDR < 0.05) with diverse functions in the cell, indicating that dopamine might act on multiple targets to promote motor neuron production. Taken together, these results demonstrate the positive effect of monoaminergic stimulation on motor neuron development and regeneration. They provide an insight into the pathways that govern the proliferation of stem/progenitor cells in the embryonic and adult spinal cord, which might contribute to the research working on enhancing adult neurogenesis in mammals.
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Moutinho, Daniela Mesquita. « Human ceruloplasmin and neurotransmitters : complex stabilization and crystallization ». Master's thesis, Faculdade de Ciências e Tecnologia, 2013. http://hdl.handle.net/10362/10853.
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Dissertation to obtain a Master Degree in Molecular Genetics and Biomedicine at Faculty of Sciences and Technology,Universidade Nova de LisboaHuman ceruloplasmin (hCp) is the molecular linker between the copper and iron metabolism and its importance in the homeostasis of human body has been implied in some neurological diseases. This plasma cuproenzyme has ferroxidase activity, oxidizing Fe2+ to Fe3+ and incorporating it into apotransferrin. hCp also has aminoxidase activity regulating the levels of amine stress hormones in the bloodstream and brain. Thus, it is thought to have an important role in neurodegenerative diseases such as Alzheimer’s or Parkinson’s. To know more about the role of cerulopalsmin on the oxidation of neurotransmitters and on brain homeostasis it is essential to know which protein residues are implied in the binding and stabilization of these neurotransmitters. The primary source of structural information for protein-ligand complexes is X-ray crystallography. This is the most successful method to determine macromolecular 3D structures but has some limitations as obtaining good diffracting protein crystals. In this study several attempts were made to achieve better hCp diffracting crystals and crystals of hcp in complex with dopamine, L-dopa, epinephrine or serotonin in order to further determine its tridimensional structure. To improve hCp stabilization and solubility, differential scanning fluorimetry and dynamic light scattering were used in a search for a better buffer for crystallization. For hCp crystallization the vapour-diffusion technique was used in combination with several other methods. Commercial crystallization screens, crystal seeding, additives, crosslinking were the several methods used to improve crystal diffraction. Co-crystallization of hCp with neurotransmitters was performed with no success. Soaking of hCp crystals with the neurotransmitters was performed in an attempt to get crystals of the hCpneurotransmitter complexes. All crystals were sent for analysis at European Synchrotron Radiation Facility (ESRF) and structural data will be further processed.
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Abdulla, Zuhair I. « Evaluating a lack of creatine in the monoaminergic neurotransmitter system ». University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1573225385280837.
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Atcherley, Christopher Wade. « Voltammetric Measurements Of Tonic And Phasic Neurotransmission ». Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/338965.
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To understand how the brain functions and what disruptions underlie neurological diseases and disorders, analytical methods are needed that can succeed in the complexity of the native brain environment. To make a measurement in functioning, live tissue, these methods must be selective for specific analytes in a matrix that has over 1000 different chemical species, be able to measure chemical changes on multiple timescales (10-3 s to 104 s), have a high spatial resolution (μm), and be sensitive (pM to μM). The work described within, details the development and application of a voltammetric method, fast-scan controlled adsorption voltammetry (FSCAV) that is capable of monitoring baseline levels of serotonin and dopamine, as well as monitoring changes on multiple time scales with high sensitivity and selectivity. Because FSCAV is performed using a carbon-fiber microelectrode, the same sensor can be used for fast-scan cyclic voltammetry to monitor rapid (phasic) changes of dopamine and serotonin in the extracellular space. Thus a single-sensor strategy for measuring tonic and phasic concentrations of these important neurotransmitters is developed and used to elucidate important insight into the differences of serotonin and dopamine regulation. Additionally it is revealed that dopamine exhibits a coaction between tonic and phasic signaling where serotonin does not. Using this approach, a method for evaluating pain processing in a preclinical model is developed, which reveals an important relationship between chronic pain and dopamine signaling. Furthermore, a mathematical model to describe mass-transport limited adsorption is developed and used to determine the diffusion coefficient of both dopamine and serotonin in situ. The work described within details an important advancement in neuroanalytical methodology that will provide new insights both short-term and long-term for studying fundamental chemical mechanisms of neurotransmission.
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Possi, Ana Paula Marques [UNESP]. « Efeitos comportamentais e neuroquímicos agudos da cafeína em ratos adolescentes e adultos ». Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/95190.
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possi_apm_me_arafo.pdf: 1001124 bytes, checksum: f27e32f6f59c4f36970ecef2dd4683a6 (MD5)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
A cafeína é provavelmente a substância psicoativa mais consumida no mundo. Essa substância está presente em alimentos, bebidas e medicamentos, sendo esses comercializados para indivíduos de todas as idades. Apesar disto, os efeitos da cafeína sobre os adolescentes são pouco compreendidos. Assim, o objetivo do presente estudo foi investigar os efeitos psicomotores e neuroquímicos da cafeína em ratos adolescentes e adultos. Para tanto, ratos Wistar adolescentes (dia pós-natal 37 - 40) ou adultos (dia pós-natal 70 - 74) tiveram sua atividade locomotora registrada após injeção intraperitoneal (i.p.) de salina ou cafeína (3, 10, 30, 60 ou 120 mg/kg). Em outro experimento ratos adolescentes e adultos receberam injeção i.p. de salina ou cafeína nas doses de 30 ou 100 mg/kg e as concentrações de dopamina, serotonina e seus metabólitos foram determinadas no córtex pré-frontal medial (CPFm), núcleo acumbens (NAc), caudado putamem (CPu) e área tegmental ventral (ATV) por cromatrografia líquida de alta resolução acoplada a detector eletroquímico. Nossos resultados demonstraram que a cafeína nas doses de 10 e 30 mg/kg induziram estimulação da atividade locomotora em ambos as idades, enquanto as doses mais elevadas (60 e 120 mg/kg) somente estimulou a atividade locomotora nos animais adolescentes. A injeção aguda de cafeína na dose de 30 e 100 mg/kg aumentou as concentrações de dopamina no CPu e na ATV em ratos adolescentes, mas não em adultos, e no NAc em ambas as idades. Além disso, cafeína causou aumento das concentrações de serotonina no CPFm em ratos adultos, mas não em adolescentes; e na ATV em ambas as idades. Portanto, em ratos adolescentes a cafeína causa estimulação em uma faixa de doses mais ampla que nos adultos. A alteração causada pela cafeína sobre o sistema dopaminérgico é mais evidente em ratos adolescentes do que adultos, enquanto...
Caffeine is the most consumed psychostimulant drug in the world. This drug is present in food, beverages and medicines marketed for individuals of all ages. Despite the great consumption of caffeine containing foods by children and adolescents, few studies investigated age related effects of caffeine. Thus, we investigated caffeine-induced locomotor activity, as well as the effects of caffeine on the dopaminergic and serotoninergic neurotransmission in adolescents and adults rats in areas important for motor behavior. Adolescent (postnatal day 37-40) or adult (postnatal day 70-74) Wistar rats had their locomotor activity registered following intraperitoneal (i.p.) injection of vehicle or caffeine (3, 10, 30, 60 or 120 mg/kg). In other experiment adolescent or adult rats received acute i.p. injections of 30 or 100 mg/kg of caffeine or saline and had the tissue levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin and 5-hydroxiindolacetic acid (5-HIAA) in the nucleus acumbens (NAc), medial pre-frontal cortex (mPFC), caudate putamen (CPu) and ventral tegmental area (VTA) quantified by high performance liquid chromatography (HPLC). Our results showed that 10 and 30 mg/kg of caffeine induced increased locomotor activity in both adolescent and adult rats, while at the higher caffeine doses (60 and 120 mg/kg) only adolescents were stimulated. The acute injection of 30 or 100 mg/kg of caffeine increased dopamine levels in the CPu and VTA in adolescent but not in adult rats, and in NAc in both ages. Furthermore, caffeine caused an increase in the concentration of serotonine in mPCF in adult but not in adolescent rats, and in VTA in both ages. Thus, in adolescent rats caffeine causes stimulation in a wider range of doses than in adults. The changes caused by caffeine on dopaminergic system are most evident in adolescent than adult rats, while... (Complete abstract click electronic access below)
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Eltayb, Amani. « Experimental studies on novel pharmacological strategies in the treatment of schizophrenia / ». Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-575-5/.
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Birgner, Carolina. « Anabolic androgenic steroids and central monoaminergic systems : Supratherapeutic doses of nandrolone decanoate affect dopamine and serotonin ». Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9208.
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Supratherapeutic doses of anabolic androgenic steroids (AASs) are administered, not only as performance-enhancing drugs in the world of sports, but also in order to modify behaviour. AAS abusers are at risk of developing serious physical and psychological side effects such as dependence and aggressive behaviour. The aim of this thesis was to investigate the impact of supratherapeutic doses of nandrolone decanoate after subchronic administration on dopamine and serotonin pathways involved in drug dependence and aggression, in the male rat brain.
Adult male Sprague-Dawley rats received intramuscular injections of nandrolone decanoate (3 or 15 mg/kg) or vehicle once daily for 14 days. Nandrolone decanoate pre-exposure abolished the effect of amphetamine on the 3,4-dihydroxyphenylacetic acid (DOPAC) tissue level in the hypothalamus and on the DOPAC/dopamine ratio in the hypothalamus and the hippocampus. A significant decrease of the basal extracellular DOPAC and homovanillic acid (HVA) levels could be detected in the nucleus accumbens, which remained low during the first hour following the amphetamine challenge. Nandrolone decanoate significantly reduced the activity of both monoamine oxidase A and B (MAO-A and -B) in the caudate putamen and amygdala. The gene transcript levels of MAO-B, and the dopamine D1 and D4 receptors were altered in limbic regions. No changes in transcriptional levels could be detected among the serotonin receptor genes examined. However, the density of the serotonin transporter protein was elevated in a range of aggression-related brain regions.
Taken together, subchronic administration of nandrolone decanoate causes dopaminergic and serotonergic dysregulations in distinct brain regions. These areas of the brain are involved in the development of drug dependence and expression of impulsive and aggressive behaviours. These results may contribute to explain some of the behavioural changes often reported in AAS abusers, such as polydrug use and impaired impulse control.
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Johnston, Louisa Clare. « An investigation of the potential antiparkinsonian activity of combined dopamine D2 and serotonin 1A receptor agonists ». Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411252.
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Matthews, Kate. « Effects of adolescent sucrose overconsumption on serotonin and dopamine signalling and associated maladaptive effects in adulthood ». Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/228732/1/Kate_Matthews_Thesis.pdf.
Texte intégralRésumé :
High sugar diet contributes to the development of obesity. Recent research suggests that the brain responds to sugar overconsumption similar to drugs of abuse. It is unknown how sugar overconsumption impacts serotonin and dopamine which are critical to the brain’s reward system. This thesis characterises an animal model of sugar overconsumption to examine the relationship between dopamine/serotonin signalling and sugar intake. Our results suggest that sugar dependence negatively influences emotional behaviour and impulse control, dopamine/serotonin signalling and production of new neurons. Understanding how sugar affects the brain will allow the development of drugs to reduce sugar intake and obesity.
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Devroye, Celine. « Role of the central serotonin subscript 2B receptor in the regulation of ascending dopaminergic pathways : relevance for the treatment of schizophrenia and drug addiction ». Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0462/document.
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Il y a quatre ans, lorsque j’ai commencé ma thèse en Neuropharmacologie, le rôle fonctionnel du récepteur serotoninergique2B (5-HT2B) central n’était guère connu. En effet, compte tenu de la mise en évidence de son expression dans le cerveau relativement récente par rapport aux autres récepteurs à la 5-HT, peu d’études avaient porté sur son impact au sein du système nerveux central. En particulier, il était établi que les récepteurs 5-HT2B, sans effet au niveau de la voie dopaminergique (DA) nigrostriée, sont capables d’exercer un contrôle tonique excitateur sur l’activité de la voie DA méso accumbale. Sur la base de cette régulation différentielle des voies DA sous-corticales, il avait été proposé que les antagonistes du récepteur 5-HT2B pourraient constituer des outils pharmacologiques pertinents pour le traitement des pathologies liées à unedysfonction du système DA et requérant une modulation indépendante des voies DA ascendantes, telles que la schizophrénie. Cependant, l’effet du blocage des récepteurs 5-HT2B au niveau de la voie DA mésocorticale, laquelle joue un rôle pivot dans le bénéfice thérapeutique des antipsychotiques (APs) atypiques,n’avait jamais été exploré. De plus, l’analyse de la littérature avait révélé que le blocage du récepteur 5-HT2B réduit les réponses neurochimiques et comportementales induites par l’amphétamine et la 3,4-méthylènedioxyméthamphétamine, suggérant que ce récepteur pourrait également représenter une cible pharmacologique intéressante pour le traitement de l’addiction. Néanmoins, la possible implication de ce récepteur dans les effets de la cocaïne, l’une des drogues les plus consommées au monde, restait alors inconnue.Ainsi, l’objectif de cette thèse était d’étudier l’influence exercée par le récepteur5-HT2B sur l’activité DA basale et activée par la cocaïne, afin de mieux évaluer le potentiel thérapeutique de ce récepteur dans le traitement de la schizophrénie et de l’addiction. A cette fin, nous avons étudié les effets de deux antagonistes puissants et sélectifs du récepteur 5-HT2B (RS 127445 et LY 266097) sur l’activité DA, en utilisant des approches biochimiques, électrophysiologiques et comportementales chez le rat.Un premier groupe d’expériences a mis en évidence l’existence d’un contrôle tonique inhibiteur exercé par le récepteur 5-HT2B sur la libération de DA dans le cortex préfrontal médian (CPFm). Ce résultat, démontrant que les récepteurs 5-HT2B régulent de manière différentielle les trois voies DA ascendantes, indique que les antagonistes du récepteur 5-HT2B présentent un profil d’action idéale pour restaurer une fonction DA normale chez les patients schizophrènes. En accord avec cette proposition, les antagonistes 5-HT2B se révèlent efficaces dans plusieurs modèles classiquement utilisés pour prédire l’efficacité des APs, alors qu’ils n’ont pas d’effet dans une tâche comportementale prédisant la tendance des APs à induire des effets secondaires moteurs. Un second groupe d’expériences visant à étudier les mécanismes sous-tendant le contrôle différentiel exercé par le récepteur 5-HT2B sur l’activité DA montre que les effets opposés induits par les antagonistes 5-HT2B sur la libération de DA dans le CPFm et le noyau accumbens (NAc) résultent d’une interaction fonctionnelle avec les récepteurs 5-HT1A exprimés dans le CPFm. Enfin, nous avons également démontré que le blocage du récepteur 5-HT2B supprime l’hyperlocomotion provoquée par la cocaïne. Cet effet, qui se produit indépendamment de la libération de DA dans le NAc et le striatum, où l’activité DA est étroitement liée aux effets comportementaux induits par la cocaïne,implique une interaction post-synaptique dans les régions DA sous-corticales. En conclusion, le travail accompli au cours des quatre années passées apporte des informations substantielles quant au rôle fonctionnel du récepteur 5-HT2Bdans la régulation des voies DA ascendantesFour years ago, at the beginning of my thesis in Neuropharmacology, the functional role of the central serotonin2B receptor (5-HT2BR) remained poorly investigated. Indeed, in light of the relatively recent discovery of its presence in the mammalian brain, as compared to other 5-HT receptors, only few studies had explored its impact within the central nervous system. Interestingly, it had been shown that 5-HT2BRs, while having no effect at the level of the nigrostriatal dopaminergic (DA) pathway, afford a tonic excitatory control on the activity of the mesoaccumbal DA tract. This differential influence on subcortical DA brain regions had led to the proposal that 5-HT2BR antagonists may be a useful tool for improved treatment of DA-related disorders requiring an independent modulation of the activity of ascending DA pathways, such ass chizophrenia. However, the effect of 5-HT2BR blockade at the level of themesocortical DA pathway, which plays a pivotal role in the the rapeutic benefit of atypical antipsychotic drugs (APDs), had never been studied. In addition,analysis of the literature revealed that 5-HT2BR blockade suppresses amphetamine and 3,4-methylenedioxymethamphetamine-induced neurochemical and behavioral responses, suggesting that this receptor may also be a relevant pharmacological target for treating drug addiction. Nevertheless,its possible implication in the effects induced by cocaine, one of the most worldwide abused drugs, remained unknown.Thus, the aim of the present thesis was to study the regulatory control exerted by the 5-HT2BR on both basal and cocaine-induced stimulation of DA activity,in order to evaluate its therapeutic relevance for improved treatment of schizophrenia and drug abuse and dependence. To this purpose, we assessed the effects of potent and selective 5-HT2BR antagonists (RS 127445 and LY266097) on DA activity, by using biochemical, electrophysiological and behavioral approaches in rats.In a first group of experiments, we found that 5-HT2BRs exert a tonic inhibitory control on DA outflow in the medial prefrontal cortex (mPFC). This finding, by showing that 5-HT2BRs afford differential controls over the three ascending DA pathways, indicates that 5-HT2BR antagonists display an ideal pattern of effects to restore normal DA function in schizophrenia. Accordingly, 5-HT2BRantagonists were efficient in several behavioral models aimed at predicting APD efficacy, and had no effect in a behavioral task reflecting APD propensity to induce motor side effects. In a second group of experiments performed to determine the mechanisms under lying the differential control exerted by 5-HT2BRs on DA activity, we demonstrated that 5-HT2BR antagonist-induced opposite effects on DA ouflow in the mPFC and the nucleus accumbens (NAc)involve a functional interplay with 5-HT1ARs expressed in the mPFC. Finally,we found that 5-HT2BR blockade suppresses cocaine-induced hyperlocomotion.This effect, which occurs independently from changes of DA outflow in theNAc and the striatum, where DA activity is tightly related to cocaine-induced behavioral responses, likely involves a post-synaptic interaction in subcorticalDA brain regions.To conclude, the work accomplished over the past four years provides substantial information with regards to the functional role of 5-HT2BRs in the regulation of the activity of ascending DA pathways. In addition, while improving the understanding of the interaction between DA and 5-HT systems,the present findings altogether highlight the therapeutic potential of 5-HT2BRantagonists for treating schizophrenia and cocaine addiction
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Gong, Li. « Co-sensitization of Dopamine and Serotonin Receptors Occurs in the Absence of a Change in the Dopamine D1 Receptor Complex After a Neonatal 6-ohda Lesion ». Digital Commons @ East Tennessee State University, 1993. https://dc.etsu.edu/etd/2686.
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To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change in the percentage of high affinity D$\sb1$ sites in these groups of rats. Striatal mRNA levels for D$\sb1$ receptors were reduced in the lesioned rats, but restored to control level after treatments with SKF 38393 in adulthood. Basal, DA-, NaF- and forskolin-stimulated adenylate cyclase activities were similar among treatment groups. Striatal DA content was reduced ($>$99%), whereas serotonin (5-HT) content was elevated ($>$50%) in the 6-OHDA groups. To study possible interaction between DA and 5-HT systems, the effects of a series of 5-HT agents on the induction of oral activity were determined. The 5-HT$\sb{\rm 1C}$ receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a marked increase in oral activity in 6-OHDA-lesioned rats. The respective 5-HT$\sb{\rm 1A}$ and 5-HT$\sb{\rm 1B}$ agonists, 8-OH-DPAT and CGS-12066B did not increase oral activity. The m-CPP-induced oral response in the lesioned rats was attenuated by mianserin, a 5-HT$\sb{\rm 1C}$ antagonist, but not by ketanserin or MDL-72222, 5-HT$\sb2$ and 5-HT$\sb3$ antagonists, respectively. Although the supersensitized oral response of lesioned rats to m-CPP was not attenuated by SCH 23390, the enhanced response of SKF 38393 was attenuated by mianserin. Additionally, mRNA levels for 5-HT$\sb{\rm 1C}$ receptor were not altered in both intact and lesioned rats. These findings demonstrate that ontogenetic treatments of neonatal 6-OHDA-lesioned rats with a D$\sb1$ agonist produce partial sensitization of DA D$\sb1$ receptors in adulthood without altered biochemical markers, and that this neonatal lesion is associated with both supersensitized DA D$\sb1$ and 5-HT$\sb{\rm 1C}$ receptors. Moreover, induction of oral activity by DA agonists is mediated via a serotonergic system.
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Wright, Alesia M. « Serotonergic and dopaminergic systems as targets for exogenous neurotoxins causing a parkinsonian syndrome ». Thesis, This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-05022009-040759/.
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Pavlopoulos, Alexandros Ikaros. « Characterization of the synaptic connectivity patterns of genetically defined neuron types in circuits that regulate dopamine and serotonin ». Thesis, KTH, Skolan för teknik och hälsa (STH), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-154201.
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The Lateral Habenula (LHb) have been implicated in both reward-seeking behavior and in depressive disorders due to its modulatory effects on dopamine rich areas. Excitatory projections from LHb target GABAergic interneurons of both ventral tegmental area (VTA) and rostromedial tegmental nucleus (RMTg) and consequently provide strong inhibition on VTA‟s dopaminergic neurons. These reward related signals are provided to LHb from distinct neuronal populations in internal Globus Pallidus (GPi). Here by using a dual viral combination of an adeno-associated helper virus (AAV) and a genetically modified rabies virus that displays specific transsynaptic retrograde spread we are providing anatomical evidence for a strong innervations of the LHb by VGLUT2+ glutaminergic and SOM+ GABAergic GPi neurons. Our results provide the first direct evidence for both an excitatory and an inhibitory projection m, from GPi to the LHb. Given the importance of the LHb as a modulatory nucleus of the dopaminergic system, the definition of its connectivity and function will give valuable insights in the understanding of both reward-seeking behavior and depressive disorders.
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Long, Hunter Wayne. « Improving Fast-Scan Cyclic Voltammetry and Raman Spectroscopy Measurements of Dopamine and Serotonin Concentrations via the Elastic Net ». Thesis, Virginia Tech, 2016. http://hdl.handle.net/10919/71679.
Texte intégralRésumé :
Dopamine and serotonin are two neurotransmitters known to both play a very important role in the human brain. For example, the death of dopamine producing neurons in a region of the brain known as the substantia nigra are known to cause the motor symptoms of Parkinson's disease. Also, many antidepressants are believed to work by increasing the extracellular level of serotonin in the brain. For the first time, it is now possible to measure the release of these two chemicals at sub-second time resolution in a human brain using a technique known as fast-scan cyclic voltammetry, for example from patients undergoing deep brain stimulation (DBS) electrode implantation surgery.
In this work, we aimed to assess the feasibility of obtaining veridical dual measurements of serotonin and dopamine from substrates with mixtures of both chemicals. In the wet lab, data was collected on known concentrations of dopamine and serotonin and then used to make models capable of estimating the concentration of both chemicals from the voltammograms recorded in the patients. A method of linear regression known as the elastic net was used to make models from the wet lab data. The wetlab data was used to compare the performance of univariate and multivariate type models over various concentration ranges from 0-8000nM of dopamine and serotonin. Cross validation revealed that the multivariate model outperformed the univariate model both in terms of the linear correlation between predictions and actual values, and pH induced noise. The pH induced noise for the univariate model was 3.4 times greater for dopamine and 4.1 times greater for serotonin than the multivariate model.
Raman spectroscopy was also investigated as a possible alternative to fast-scan cyclic voltammetry. Raman spectroscopy could have several benefits over fast-scan cyclic voltammetry, including the ability to chronically implant the measurement probe into a patient's brain and make observations over a long period of time. Raman spectroscopy data was collected on known concentrations of dopamine to investigate its potential in making in vivo measurements, however this data collection failed. Therefore, simulations were made which revealed the potential of the elastic net algorithm to determine the Raman spectra of several neurotransmitters simultaneously, even when they are in mixtures and the spectra are obstructed by the noisy background. The multivariate type model outperformed the univariate type model on Raman spectroscopy data and was able to predict dopamine with an error of 805nM RMS and serotonin with an error of 475nM RMS after being trained on concentrations smaller than 5uM of both dopamine and serotonin. In addition, the original Raman spectra of both neurotransmitters was extracted from the noise and reproduced very accurately by this method.Master of Science
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Nevalainen, Nina. « Dysfunction in the nigrostriatal system : effects of L-DOPA and GDNF ». Doctoral thesis, Umeå universitet, Histologi med cellbiologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-64149.
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Parkinson’s disease is a common neurodegenerative disorder caused by nigrostriatal dopamine loss, with motor deficiencies as the primary outcome. To increase the striatal dopamine content, patients are treated with 3,4-dihydroxyphenyl-l-alanine (l-DOPA). Beneficial relief of the motor symptoms is achieved initially, although the efficacy is lost with time and severe side effects, referred to as l-DOPA-induced dyskinesia, manifest in the majority of patients. Biological mechanisms responsible for the dopaminergic degeneration and the upcoming of dyskinesia are still unclear, and thus knowledge regarding critical factors for maintenance of the nigrostriatal system as well as neurochemical changes upon chronic l-DOPA is urgent. The present work aims at studying the importance of glial cell line-derived neurotrophic factor (GDNF) for nigrostriatal preservation, and the involvement of the dopaminergic, serotonergic, and glutamatergic systems in l-DOPA-induced dyskinesia. Effects from different levels of GDNF expression were evaluated on fetal mouse nigrostriatal tissue in a grafting study. In GDNF gene-deleted grafts, degeneration of the entire nigrostriatal system was evident at 6 months. In grafts with partial GDNF expression, significant loss of dopamine neurons was observed at later time points, although deviant findings in the dopamine integrity such as reduced innervation capacity and presence of intracellular inclusions-like structures were already present at earlier stages. The results emphasize GDNF as a crucial factor for long-term maintenance of the nigrostriatal system. Furthermore, striatal neurochemical alterations upon chronic l-DOPA treatment were studied in hemiparkinsonian rats using in vivo voltametry. The findings demonstrated impaired dopamine as well as glutamate releases in dyskinetic subjects, with no effects from acute l-DOPA administration. Conversely, in l-DOPA naïve dopamine-lesioned animals, dopamine release was increased and glutamate release attenuated upon a l-DOPA challenge. Moreover, l-DOPA-derived dopamine release was demonstrated to originate from serotonergic nerve fibers in the dopamine-lesioned striatum, an event that contributes significantly to dopamine levels also in intact striatum, and thus, is not a consequence from dopamine depletion. Assessment of serotonergic nerve fibers in l-DOPA treated animals and in a grafting study concluded that nerve fiber density was not affected by chronic l-DOPA treatment, nevertheless, dysfunction of this system can be suspected in dyskinetic animals since dopamine release was impaired and regulation of glutamate release by serotonergic 5-HT1A receptor activation was achieved in normal but not in dyskinetic animals. Furthermore, the selective serotonin reuptake inhibitor, fluoxetine, attenuated l-DOPA-induced dyskientic behavior, an effect that was demonstrated to be mediated via 5-HT1A receptors. In conclusion, dysmodulation of multiple transmitter systems is evident in LID.
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Andreatta, Gabriele. « Dormancy awakened : aminergic control of diapause in Drosophila ». Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3424143.
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Coping with adverse environmental conditions is one of the most crucial challenges for all living beings. The coupling between external cues and hormonal signaling is key to allow survivorship of individuals and insects in particular have been intensively studied to better understand this connection. Although the hormonal cascade that promotes insect development and reproduction is well known (insulin signaling - juvenile hormone – 20-Ecdysone), how this neuroendocrine axis is modulated by environmental stimuli remains still largely elusive. To deepen the molecular features of IIS-JH-20E axis regulation, we focused our attention on one of the best examples of physiological strategies triggered by environmental stimuli, diapause. Diapause is an inducible developmental arrest, which characterizes the life cycle of several species, from Caenorhabditis elegans to mammals. Our results shed new light on the regulation of key neuroendocrine pathways for growth and development, and suggest how organisms couple environmental conditions with inner hormonal physiology.Sopravvivere a drastici cambiamenti climatici rappresenta una delle sfide principali per gli esseri viventi. Gli insetti non solo forniscono esempi straordinari di adattamenti morfologici e fisiologici a climi sfavorevoli, ma sono anche molto studiati per comprendere quali sono i meccanismi molecolari responsabili di questi adattamenti. Negli insetti, i principali processi ormonali che promuovono lo sviluppo e la riproduzione sono ben noti e comprendono tre attori principali, il segnale insulinico (IIS), l’ormone giovanile (JH) e l’idrossi-ecdisone (20E). Nonostante questo importante asse neuroendocrino (IIS-JH-20E) sia ben studiato, poco si conosce riguardo i meccanismi molecolari che trasducono le informazioni ambientali ai componenti fondamentali del sistema endocrino, modulandone l’attività regolatoria. Per questo abbiamo rivolto la nostra attenzione ad uno degli esempi più interessanti di strategie fisiologiche evocate dagli stimoli esterni, la diapausa, un arresto dello sviluppo inducibile che rappresenta un evento estremamente diffuso nel regno animale. I nostri risultati forniscono un contributo alla comprensione degli aspetti regolativi dei meccanismi neuroendocrini fondamentali per la crescita, lo sviluppo e la riproduzione, e suggeriscono alcune modalità con le quali gli insetti accoppiano la percezione delle condizioni ambientali con la loro fisiologia ormonale.
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Svensson, Erik. « Modulatory effects and interactions of substance P, dopamine, and 5-HT in a neuronal network / ». Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-524-7/.
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Chou, Yuan-Hwa. « A PET study on dopamine and serotonin receptor binding in the primate brain : challenges with antipsychotic drugs and amphetamine / ». Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4639-6/.
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Plach, Michael [Verfasser], Kristina [Akademischer Betreuer] Friedland et Kristina [Gutachter] Friedland. « Serotonin 5-HT2A - Dopamine D2 Receptor Heterodimers : Characterization and Functional Evaluation / Michael Plach ; Gutachter : Kristina Friedland ; Betreuer : Kristina Friedland ». Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1218300876/34.
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Bjørnebekk, Astrid. « On antidepressant effects of running and SSRI : focus on hippocampus and striatal dopamine pathways / ». Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-246-0/.
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Kostrzewa, Richard M., John P. Kostrzewa, Russell W. Brown, Przemyslaw Nowak et University of Silesia Ryszard Brus Medical. « Dopamine Receptor Supersensitivity : Development, Mechanisms, Presentation, and Clinical Applicability ». Digital Commons @ East Tennessee State University, 2008. https://doi.org/10.1007/BF03033804.
Texte intégralRésumé :
The process of receptor supersensitivity (RSS) has a long history and is an epiphenomenon of neuronal denervation. Dopamine (DA) RSS (DARSS) similarly occurs after DA denervation, and this process is invoked in neuropsychiatric and neurodegenerative disorders. From studies largely over the past 25 years, much has been learned regarding DARSS. For example, overt D1 DARSS occurs after perinatal destruction of nigrostriatal DA fibers. However, following perinatal destruction of DA innervation, the most-prominent behavioral effects of a D1 agonist are observed after a series of D1 agonist treatments--a process known as priming of D1 DA receptors. Moreover, perinatal lesioning of DA fibers produces prominent serotonin (5-HT) RSS, and in fact 5-HT RSS appears to modulate D1 DA RSS. In rodents, receptor supersensitization by these means appears to be irreversible. In contrast to the observed D1 DARSS, D2 DARSS apparently does not occur after perinatal DA denervation. Also, while repeated D1 agonist treatment of intact rats has no observable effect, repeated D2 agonist treatments, during or after the ontogenetic phase, produces prominent life-long D2 RSS. The process may have an association with substance abuse. Therefore, production of D1 and D2 DARSS occurs by different means and under different circumstances, and in association with perhaps different neuronal phenotypes, and with greater incidence in either intact (D2) or DA-lesioned counterparts (D1). The physiological consequence of RSS are multiple.