Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence

Marcy J. Bubar, Kathryn Cunningham

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The development of novel pharmacological agents for the treatment of psychostimulant use disorders is an important research imperative. One potential target system that has been largely overlooked is the serotonin (5-HT) neurotransmitter system. Preclinical studies indicate that 5-HT may be important in modulating the reinforcing properties of various drugs of abuse. While the potential sites of action of 5-HT within the brain are extensive, the natural starting point to examine the mechanisms by which 5-HT may be useful in treatment of psychostimulant use disorders is the interaction between 5-HT and dopamine (DA), a primary mediator of the "rewarding" effects of psychstimulants. Two key modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2AR) and the 5-HT2CR. These receptors are known to control the neurochemical and behavioral effects of psychostimulants, and in particular, the in vivo effects of cocaine. Preclinical studies indicate that 5-HT2AR antagonists and/or 5-HT2CR agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT2CR agonists may also effectively reduce cocaine intake in active cocaine users. At present the progression of studies to probe the effectiveness of 5-HT2AR and 5-HT2CR ligands in the clinical setting is hindered by a lack of available selective 5-HT2AR antagonists or 5-HT2CR agonists for use in human cocaine abusers. However, a number of selective 5-HT2R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.

Original languageEnglish (US)
Pages (from-to)1971-1985
Number of pages15
JournalCurrent Topics in Medicinal Chemistry
Volume6
Issue number18
DOIs
StatePublished - Oct 2006

Fingerprint

Receptor, Serotonin, 5-HT2C
Serotonin
Receptor, Serotonin, 5-HT2A
Modulation
Cocaine
Dopamine
Ligands
Street Drugs
Nervous System Diseases
Modulators
Action Potentials
Substance-Related Disorders
Neurotransmitter Agents
Psychiatry
Brain
Clinical Trials
Pharmacology
Recurrence
Research

Keywords

  • Conditioned place preference (CPP)
  • Dopamine
  • Locomotor hyperactivity
  • Neurotransmitter system
  • Serotonin reuptake transporter (SERT)

ASJC Scopus subject areas

  • Medicine(all)
  • Chemistry(all)

Cite this

Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence. / Bubar, Marcy J.; Cunningham, Kathryn.

In: Current Topics in Medicinal Chemistry, Vol. 6, No. 18, 10.2006, p. 1971-1985.

Research output: Contribution to journalArticle

@article{d1e956bbc5784696b596d174cbb474e9,
title = "Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence",
abstract = "The development of novel pharmacological agents for the treatment of psychostimulant use disorders is an important research imperative. One potential target system that has been largely overlooked is the serotonin (5-HT) neurotransmitter system. Preclinical studies indicate that 5-HT may be important in modulating the reinforcing properties of various drugs of abuse. While the potential sites of action of 5-HT within the brain are extensive, the natural starting point to examine the mechanisms by which 5-HT may be useful in treatment of psychostimulant use disorders is the interaction between 5-HT and dopamine (DA), a primary mediator of the {"}rewarding{"} effects of psychstimulants. Two key modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2AR) and the 5-HT2CR. These receptors are known to control the neurochemical and behavioral effects of psychostimulants, and in particular, the in vivo effects of cocaine. Preclinical studies indicate that 5-HT2AR antagonists and/or 5-HT2CR agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT2CR agonists may also effectively reduce cocaine intake in active cocaine users. At present the progression of studies to probe the effectiveness of 5-HT2AR and 5-HT2CR ligands in the clinical setting is hindered by a lack of available selective 5-HT2AR antagonists or 5-HT2CR agonists for use in human cocaine abusers. However, a number of selective 5-HT2R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.",
keywords = "Conditioned place preference (CPP), Dopamine, Locomotor hyperactivity, Neurotransmitter system, Serotonin reuptake transporter (SERT)",
author = "Bubar, {Marcy J.} and Kathryn Cunningham",
year = "2006",
month = "10",
doi = "10.2174/156802606778522131",
language = "English (US)",
volume = "6",
pages = "1971--1985",
journal = "Current Topics in Medicinal Chemistry",
issn = "1568-0266",
publisher = "Bentham Science Publishers B.V.",
number = "18",

}

TY - JOUR

T1 - Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence

AU - Bubar, Marcy J.

AU - Cunningham, Kathryn

PY - 2006/10

Y1 - 2006/10

N2 - The development of novel pharmacological agents for the treatment of psychostimulant use disorders is an important research imperative. One potential target system that has been largely overlooked is the serotonin (5-HT) neurotransmitter system. Preclinical studies indicate that 5-HT may be important in modulating the reinforcing properties of various drugs of abuse. While the potential sites of action of 5-HT within the brain are extensive, the natural starting point to examine the mechanisms by which 5-HT may be useful in treatment of psychostimulant use disorders is the interaction between 5-HT and dopamine (DA), a primary mediator of the "rewarding" effects of psychstimulants. Two key modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2AR) and the 5-HT2CR. These receptors are known to control the neurochemical and behavioral effects of psychostimulants, and in particular, the in vivo effects of cocaine. Preclinical studies indicate that 5-HT2AR antagonists and/or 5-HT2CR agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT2CR agonists may also effectively reduce cocaine intake in active cocaine users. At present the progression of studies to probe the effectiveness of 5-HT2AR and 5-HT2CR ligands in the clinical setting is hindered by a lack of available selective 5-HT2AR antagonists or 5-HT2CR agonists for use in human cocaine abusers. However, a number of selective 5-HT2R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.

AB - The development of novel pharmacological agents for the treatment of psychostimulant use disorders is an important research imperative. One potential target system that has been largely overlooked is the serotonin (5-HT) neurotransmitter system. Preclinical studies indicate that 5-HT may be important in modulating the reinforcing properties of various drugs of abuse. While the potential sites of action of 5-HT within the brain are extensive, the natural starting point to examine the mechanisms by which 5-HT may be useful in treatment of psychostimulant use disorders is the interaction between 5-HT and dopamine (DA), a primary mediator of the "rewarding" effects of psychstimulants. Two key modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2AR) and the 5-HT2CR. These receptors are known to control the neurochemical and behavioral effects of psychostimulants, and in particular, the in vivo effects of cocaine. Preclinical studies indicate that 5-HT2AR antagonists and/or 5-HT2CR agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT2CR agonists may also effectively reduce cocaine intake in active cocaine users. At present the progression of studies to probe the effectiveness of 5-HT2AR and 5-HT2CR ligands in the clinical setting is hindered by a lack of available selective 5-HT2AR antagonists or 5-HT2CR agonists for use in human cocaine abusers. However, a number of selective 5-HT2R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence.

KW - Conditioned place preference (CPP)

KW - Dopamine

KW - Locomotor hyperactivity

KW - Neurotransmitter system

KW - Serotonin reuptake transporter (SERT)

UR - http://www.scopus.com/inward/record.url?scp=33749506018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749506018&partnerID=8YFLogxK

U2 - 10.2174/156802606778522131

DO - 10.2174/156802606778522131

M3 - Article

VL - 6

SP - 1971

EP - 1985

JO - Current Topics in Medicinal Chemistry

JF - Current Topics in Medicinal Chemistry

SN - 1568-0266

IS - 18

ER -