The role of 5-HT3 receptors in drug abuse and as a target for pharmacotherapy

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)454-467
Number of pages14
JournalCNS and Neurological Disorders - Drug Targets
Volume7
Issue number5
DOIs
StatePublished - 2008

Fingerprint

Receptors, Serotonin, 5-HT3
Substance-Related Disorders
Drug Therapy
Self Administration
Street Drugs
Neurotransmitter Agents
Dopamine
Tegmentum Mesencephali
Alcohols
Pharmacology
Ventral Tegmental Area
Serotonin Receptors
Nucleus Accumbens
Amygdala
Reward
Ion Channels
Developed Countries
Synaptic Transmission
Alcohol Drinking
Alcoholism

Keywords

  • Addictions
  • Amphetamine
  • Cocaine
  • Dopamine
  • Ethanol
  • Nicotine
  • Opiates
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology
  • Medicine(all)

Cite this

@article{cdd632a466954fd49aa445b7dd2468d5,
title = "The role of 5-HT3 receptors in drug abuse and as a target for pharmacotherapy",
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 = "Addictions, Amphetamine, Cocaine, Dopamine, Ethanol, Nicotine, Opiates, Serotonin",
author = "Eric Engleman and Zachary Rodd and Richard Bell and Murphy, {J. M.}",
year = "2008",
doi = "10.2174/187152708786927886",
language = "English",
volume = "7",
pages = "454--467",
journal = "CNS and Neurological Disorders - Drug Targets",
issn = "1871-5273",
publisher = "Bentham Science Publishers B.V.",
number = "5",

}

TY - JOUR

T1 - The role of 5-HT3 receptors in drug abuse and as a target for pharmacotherapy

AU - Engleman, Eric

AU - Rodd, Zachary

AU - Bell, Richard

AU - Murphy, J. M.

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Addictions

KW - Amphetamine

KW - Cocaine

KW - Dopamine

KW - Ethanol

KW - Nicotine

KW - Opiates

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=61549106960&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61549106960&partnerID=8YFLogxK

U2 - 10.2174/187152708786927886

DO - 10.2174/187152708786927886

M3 - Article

C2 - 19128203

AN - SCOPUS:61549106960

VL - 7

SP - 454

EP - 467

JO - CNS and Neurological Disorders - Drug Targets

JF - CNS and Neurological Disorders - Drug Targets

SN - 1871-5273

IS - 5

ER -