Abstract
Alcohol and drug abuse continue to be a major public health problem in the United States and other industrialized nations. Extensive preclinical research indicates the mesolimbic dopamine (DA) pathway and associated regions mediate the rewarding and reinforcing effects of drugs of abuse and natural rewards, such as food and sex. The serotonergic (5-HT) system, in concert with others neurotransmitter systems, plays a key role in modulating neuronal systems within the mesolimbic pathway. A substantial portion of this modulation is mediated by activity at the 5-HT3 receptor. The 5- HT3 receptor is unique among the 5-HT receptors in that it directly gates an ion channel inducing rapid depolarization that, in turn, causes the release of neurotransmitters and/or peptides. Preclinical findings indicate that antagonism of the 5- HT3 receptor in the ventral tegmental area, nucleus accumbens or amygdala reduces alcohol self-administration and/or alcohol- associated effects. Less is known about the effects of 5-HT3 receptor activity on the self-administration of other drugs of abuse or their associated effects. Clinical findings parallel the preclinical findings such that antagonism of the 5- HT3 receptor reduces alcohol consumption and some of its subjective effects. This review provides an overview of the structure, function, and pharmacology of 5-HT3 receptors, the role of these receptors in regulating DA neurotransmission in mesolimbic brain areas, and discusses data from animal and human studies implicating 5-HT3 receptors as targets for the development of new pharmacological agents to treat addictions.
Keywords: Serotonin, dopamine, ethanol, cocaine, nicotine, amphetamine, opiates, addictions
CNS & Neurological Disorders - Drug Targets
Title: The Role of 5-HT3 Receptors in Drug Abuse and as a Target for Pharmacotherapy
Volume: 7 Issue: 5
Author(s): E. A. Engleman, Z. A. Rodd, R. L. Bell and J. M. Murphy
Affiliation:
Keywords: Serotonin, dopamine, ethanol, cocaine, nicotine, amphetamine, opiates, addictions
Abstract: Alcohol and drug abuse continue to be a major public health problem in the United States and other industrialized nations. Extensive preclinical research indicates the mesolimbic dopamine (DA) pathway and associated regions mediate the rewarding and reinforcing effects of drugs of abuse and natural rewards, such as food and sex. The serotonergic (5-HT) system, in concert with others neurotransmitter systems, plays a key role in modulating neuronal systems within the mesolimbic pathway. A substantial portion of this modulation is mediated by activity at the 5-HT3 receptor. The 5- HT3 receptor is unique among the 5-HT receptors in that it directly gates an ion channel inducing rapid depolarization that, in turn, causes the release of neurotransmitters and/or peptides. Preclinical findings indicate that antagonism of the 5- HT3 receptor in the ventral tegmental area, nucleus accumbens or amygdala reduces alcohol self-administration and/or alcohol- associated effects. Less is known about the effects of 5-HT3 receptor activity on the self-administration of other drugs of abuse or their associated effects. Clinical findings parallel the preclinical findings such that antagonism of the 5- HT3 receptor reduces alcohol consumption and some of its subjective effects. This review provides an overview of the structure, function, and pharmacology of 5-HT3 receptors, the role of these receptors in regulating DA neurotransmission in mesolimbic brain areas, and discusses data from animal and human studies implicating 5-HT3 receptors as targets for the development of new pharmacological agents to treat addictions.
Export Options
About this article
Cite this article as:
Engleman A. E., Rodd A. Z., Bell L. R. and Murphy M. J., The Role of 5-HT3 Receptors in Drug Abuse and as a Target for Pharmacotherapy, CNS & Neurological Disorders - Drug Targets 2008; 7 (5) . https://dx.doi.org/10.2174/187152708786927886
DOI https://dx.doi.org/10.2174/187152708786927886 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Simultaneous Interruption of Signal Transduction and Cell Cycle Regulatory Pathways: Implications for New Approaches to the Treatment of Childhood Leukemias
Current Drug Targets Cardiac Remodeling Induced by Smoking: Concepts, Relevance, and Potential Mechanisms
Inflammation & Allergy - Drug Targets (Discontinued) Gene Expression Profiling in Rodent Models for Schizophrenia
Current Neuropharmacology The Many Roles of Statins in Ischemic Stroke
Current Neuropharmacology What About the Neuroimaging Findings in Social Anxiety Disorder?
Reviews on Recent Clinical Trials Natural Sourced Inhibitors of EGFR, PDGFR, FGFR and VEGFRMediated Signaling Pathways as Potential Anticancer Agents
Current Medicinal Chemistry Neuropeptide Y: Role in Emotion and Alcohol Dependence
CNS & Neurological Disorders - Drug Targets The Control of Endoplasmic Reticulum-Initiated Apoptosis by the BCL-2 Family of Proteins
Current Molecular Medicine Kleptomania: Differential Diagnosis and Treatment Modalities
Current Psychiatry Reviews Dopamine Thioethers in Neurodegeneration
Current Topics in Medicinal Chemistry Discovery of GPCR Ligands by Molecular Docking Screening: Novel Opportunities Provided by Crystal Structures
Current Topics in Medicinal Chemistry East Meets West in the Search for Alzheimers Therapeutics - Novel Dimeric Inhibitors from Tacrine and Huperzine A
Current Alzheimer Research Regulation of MAPK Signaling Pathways Through Immunophilin-ligand Complex
Current Topics in Medicinal Chemistry Neuronal Plasticity, Stress and Depression: Involvement of the Cytoskeletal Microtubular System?
Current Drug Targets - CNS & Neurological Disorders Characterization of Cancer Stem Cells and Primary Cilia in Medulloblastoma
CNS & Neurological Disorders - Drug Targets Low-Temperature Thermal Properties of Channel Water Confined in Nanopores with Hydrophilic Crystalline and Silica Non-Crystalline Walls
Current Inorganic Chemistry (Discontinued) Leukocyte Traffic Blockade as a Therapeutic Strategy in Inflammatory Bowel Disease
Current Drug Targets Cognitive and Psychomotor Performance During Alcohol Hangover
Current Drug Abuse Reviews Platelet SERT as a Peripheral Biomarker of Serotonergic Neurotransmission in the Central Nervous System
Current Medicinal Chemistry Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis
Current Pharmaceutical Design