Role of 5-HT6 Receptor in Conditioned Learning and Memory

Role of 5-HT6 Receptor in Conditioned Learning and Memory
Author: Susie Woods
Publisher:
Total Pages:
Release: 2011
Genre:
ISBN:

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The recently discovered 5-HT6 receptor has generated interest due to increasing evidence for its role in feeding, obesity, anxiety, depression and cognition. Initial studies utilising selective 5-HT6 receptor antagonists found pro-cognitive effects in various cognitive paradigms. In the last three years selective 5-HT6 receptor agonists have been developed and initial reports suggested they impaired cognition as predicted, but more recent reports have found paradoxical pro-cognitive effects in learning and memory tasks. The main aim of the current thesis was to determine the role of the 5-HT6 receptor in a conditioned emotion response (CER) task in rats. Both the effects of 5-HT6 receptor antagonists and agonists given alone, and their abilities to reverse a cholinergic- or glutamatergic-induced memory impairment were analysed. Secondly, to analyse the intracellular mechanisms involved in the behavioural effects exerted following treatment with 5-HT6 receptor ligands by examining changes in hippocampal protein expression. Pre-treatment with either the muscarinic receptor antagonist, scopolamine, or the NMDA receptor antagonist, MK-801, induced memory impairment in the 24 hour retention trial. Post-training administration of 5-HT6 receptor antagonist, SB-271046, and agonists, EMD 386088 and E-6801, had little effect on CER-induced behaviour when given alone, but both reversed the cholinergic- and glutamatergic-induced deficits. Western blot analysis revealed no significant difference between hippocampal BDNF and 5-HT6 receptor protein levels following any drug or shock treatment, but some interesting trends were observed. CER slightly increased BDNF expression, this was reduced by scopolamine and MK-801 which in turn was reversed with SB-271046 and EMD 386088. CER decreased 5-HT6 receptor expression, scopolamine caused further reduction, SB-271046 and EMD 386088 increased the expression following scopolamine. MK-801 increased 5-HT6 receptor expression, whilst SB-271046 further enhanced this expression, EMD 386088 reduced it. No significant results were observed in the proteomic studies. These findings provide further evidence for the exciting potential therapeutic use of 5-HT6 receptor compounds in the treatment of cognitive dysfunction.

Pharmacology of 5-HT6 Receptors

Pharmacology of 5-HT6 Receptors
Author: Franco Borsini
Publisher: Academic Press
Total Pages: 400
Release: 2010
Genre: Medical
ISBN: 9780123849762

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The serotonin 5-HT receptor represents a novel pharmacological target whose impact on physiopathology of CNS functions remains undertermined. Since its discovery in 1993, interest has grown rapidly: from 10 publications over the following two years, there are now over 250 articles on this topic. Precisely on account of the rise in the number of researchers working in this field, however, and the variety of different experimental settings in which this research has, and is being undertaken, this information appears fragmented and inconsistent. This volume of International Review of Neurobiology is the first of two volumes representing the only comprehensive attempt to summarize the research data so far obtained in the rapidly growing field of 5-HT receptors, to evidence the state-of-the-art in the field of 5-HT receptor physiology and pharmacology and to account for some of the inconsistencies in the information available. Cover illustration: Striatal neuronal subtype-specific expression of functionally characterized 5-HT receptors. Cartoon of a simplified representation of the physiology of striatum. Three neuronal subtypes are represented: GABAergic fast-spiking interneurons (FSi), cholinergic intermeurons, and medium spiny neurons (MSN), the GABAergic projection neurons. The recently characterized functional expression of 5-HT receptor subtypes in FSi (Blomeley and Bracci, 2009) and cholinergic interneurons (Bonsi et al., 2007) is depicted. Similar electrophysiological studies on MSN are still lacking Credit: Antonio Pisani, Department of Neuroscience, University Tor Vergata, Rome, Italy and Annalisa Tassone, Graziella Madeo, Giuseppe Sciamanna, Paola Bonsi, Laboratory of Neurophysiology and Plasticity, I.R.C.C.S. Fondazione Santa Lucia, Italy.

Pharmacology of 5-HT6 receptors, Part I

Pharmacology of 5-HT6 receptors, Part I
Author:
Publisher: Academic Press
Total Pages: 0
Release: 2010-11-29
Genre: Science
ISBN: 9780123849762

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The serotonin 5-HT6 receptor represents a novel pharmacological target whose impact on physiopathology of CNS functions remains undetermined. Some receptor antagonists have been synthesized and they show a modulatory role in learning and memory processes and food intake. The pharmacology of 5-HT6 receptor agonists is still under evaluation. However, both 5-HT6 antagonists and agonists seem to exert potential antidepressant activity. Recently, a second messenger system has been discovered. 5-HT6 receptor function is becoming more and more intriguing. Thus, the aim of the present book is to try to clarify the pharmacology of 5-HT6 receptors.

Handbook of Neurochemistry

Handbook of Neurochemistry
Author: Abel Lajtha
Publisher:
Total Pages:
Release: 1982
Genre: Neurochemistry
ISBN:

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Animal Models of Cognitive Impairment

Animal Models of Cognitive Impairment
Author: Edward D. Levin
Publisher: CRC Press
Total Pages: 395
Release: 2006-06-22
Genre: Medical
ISBN: 1420004336

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The costs associated with a drug's clinical trials are so significant that it has become necessary to validate both its safety and efficacy in animal models prior to the continued study of the drug in humans. Featuring contributions from distinguished researchers in the field of cognitive therapy research, Animal Models of Cognitive Impairmen

Pharmacology of 5-HT6 Receptors

Pharmacology of 5-HT6 Receptors
Author: Franco Borsini
Publisher: Academic Press
Total Pages: 248
Release: 2011
Genre: Central nervous system
ISBN: 0123859026

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Annotation The serotonin 5-HT6 receptor represents a novel pharmacological target whose impact on physiopathology of CNS functions remains undetermined. Some receptor antagonists have been synthesized and they show a modulatory role in learning and memory processes and food intake.

The Role of 5-HT Systems on Memory and Dysfunctional Memory

The Role of 5-HT Systems on Memory and Dysfunctional Memory
Author: Alfredo Meneses
Publisher: Academic Press
Total Pages: 95
Release: 2014-03-11
Genre: Science
ISBN: 0128010835

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Drugs acting through 5-HT (5-hydroxytryptamine, or serotonin) systems modulate memory and its alterations, but the mechanisms by which they do so are poorly understood. Agonists and antagonists for 5-HT receptors, as well as serotonin uptake inhibitors, present promnesic (memory-promoting) and/or anti-amnesic effects under different conditions, and 5-HT receptors are also associated with neural changes. The Role of 5-HT Systems on Memory and Dysfunctional Memory: Emergent Targets for Memory Formation and Memory Alterations reviews and summarizes the most recent research related to 5-HT drugs and the mechanisms by which they effect alterations in memory. This latest evidence is reviewed in the context of memory deficits related to brain disorders, such as post-traumatic stress disorder, schizophrenia, post-stroke cognitive dysfunctions, Parkinson’s disease, and infection-induced memory impairments. Written by an expert in the field of memory, The Role of 5-HT Systems on Memory and Dysfunctional Memory provides an introduction to the latest research on 5-HT receptors and their contributions to the physiological and pharmacological basis of memory. Examines and summarizes the recent advances in drugs that act through the 5-HT systems Reviews findings in the context of brain disorders that involve memory deficits Covers emergent targets for memory formation and memory alterations

Handbook of the Behavioral Neurobiology of Serotonin

Handbook of the Behavioral Neurobiology of Serotonin
Author: Christian P. Muller
Publisher: Academic Press
Total Pages: 849
Release: 2009-12-30
Genre: Science
ISBN: 0080878172

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Serotonin (5-hydroxytryptamine, often cited as 5-HT) is one of the major excitatory neurotransmitter, and the serotonergic system is one of the best studied and understood transmitter systems. It is crucially involved in the organization of virtually all behaviours and in the regulation of emotion and mood. Alterations in the serotonergic system, induced by e.g. learning or pathological processes, underlie behavioural plasticity and changes in mood, which can finally results in abnormal behaviour and psychiatric conditions. Not surprisingly, the serotonergic system and its functional components appear to be targets for a multitude of pharmacological treatments - examples of very successful drugs targeting the serotoninergic system include Prozac and Zoloft. The last decades of research have not only fundamentally expanded our view on serotonin but also revealed in much more detail an astonishing complexity of this system, which comprises a multitude of receptors and signalling pathways. A detailed view on its role in basal, but also complex, behaviours emerged, and, was presented in a number of single review articles. Although much is known now, the serotonergic system is still a fast growing field of research contributing to our present understanding of the brains function during normal and disturbed behaviour. This handbook aims towards a detailed and comprehensive overview over the many facets of behavioural serotonin research. As such, it will provide the most up to date and thorough reading concerning the serotonergic systems control of behaviour and mood in animals and humans. The goal is to create a systematic overview and first hand reference that can be used by students and scholars alike in the fields of genetics, anatomy, pharmacology, physiology, behavioural neuroscience, pathology, and psychiatry. The chapters in this book will be written by leading scientists in this field. Most of them have already written excellent reviews in their field of expertise. The book is divided in 4 sections. After an historical introduction, illustrating the growth of ideas about serotonin function in behaviour of the last forty years, section A will focus on the functional anatomy of the serotonergic system. Section B provides a review of the neurophysiology of the serotonergic system and its single components. In section C the involvement of serotonin in behavioural organization will be discussed in great detail, while section D deals with the role of serotonin in behavioural pathologies and psychiatric disorders. The first handbook broadly discussing the behavioral neurobiology of the serotonorgic transmitter system Co-edited by one of the pioneers and opinion leaders of the past decades, Barry Jacobs (Princeton), with an international list (10 countries) of highly regarded contributors providing over 50 chapters, and including the leaders in the field in number of articles and citations: K. P. Lesch, T. Sharp, A. Caspi, P. Blier, G.K. Aghajanian, E. C. Azmitia, and others The only integrated and complete resource on the market containing the best information integrating international research, providing a global perspective to an international community Of great value not only for researchers and experts, but also for students and clinicians as a background reference