Group III metabotropic glutamate receptors and drug addiction

Limin Mao, Minglei Guo, Daozhong Jin, Bing Xue, John Q. Wang

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates).

Original languageEnglish (US)
Pages (from-to)445-451
Number of pages7
JournalFrontiers of Medicine in China
Volume7
Issue number4
DOIs
StatePublished - Dec 23 2013

Fingerprint

Metabotropic Glutamate Receptors
Substance-Related Disorders
Opiate Alkaloids
Basal Ganglia
Pharmaceutical Preparations
Alcohols
Drug-Seeking Behavior
Presynaptic Receptors
Ionotropic Glutamate Receptors
Autoreceptors
Limbic System
Street Drugs
Amphetamine
Reward
Cocaine
Synapses
Glutamic Acid
Dopamine
Homeostasis
Mutation

Keywords

  • alcohol
  • amphetamine
  • cocaine
  • group III metabotropic glutamate receptors
  • opiate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Group III metabotropic glutamate receptors and drug addiction. / Mao, Limin; Guo, Minglei; Jin, Daozhong; Xue, Bing; Wang, John Q.

In: Frontiers of Medicine in China, Vol. 7, No. 4, 23.12.2013, p. 445-451.

Research output: Contribution to journalReview article

Mao, Limin ; Guo, Minglei ; Jin, Daozhong ; Xue, Bing ; Wang, John Q. / Group III metabotropic glutamate receptors and drug addiction. In: Frontiers of Medicine in China. 2013 ; Vol. 7, No. 4. pp. 445-451.
@article{db28b3ff150c4e1e934e2f8a40c72965,
title = "Group III metabotropic glutamate receptors and drug addiction",
abstract = "Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates).",
keywords = "alcohol, amphetamine, cocaine, group III metabotropic glutamate receptors, opiate",
author = "Limin Mao and Minglei Guo and Daozhong Jin and Bing Xue and Wang, {John Q.}",
year = "2013",
month = "12",
day = "23",
doi = "10.1007/s11684-013-0291-1",
language = "English (US)",
volume = "7",
pages = "445--451",
journal = "Frontiers of Medicine",
issn = "2095-0217",
publisher = "Springer Science + Business Media",
number = "4",

}

TY - JOUR

T1 - Group III metabotropic glutamate receptors and drug addiction

AU - Mao, Limin

AU - Guo, Minglei

AU - Jin, Daozhong

AU - Xue, Bing

AU - Wang, John Q.

PY - 2013/12/23

Y1 - 2013/12/23

N2 - Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates).

AB - Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are linked to persistent drug addiction. Accumulating data have demonstrated roles of ionotropic glutamate receptors and group I and II metabotropic glutamate receptors (mGluRs) in this event. Emerging evidence also identifies Gαi/o-coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as direct substrates of drugs of abuse and active regulators of drug action. Auto- and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of glutamatergic corticostriatal and GABAergic striatopallidal pathways, respectively. These presynaptic receptors regulate basal and/or phasic release of respective transmitters to maintain basal ganglia homeostasis. In response to operant administration of common addictive drugs, such as psychostimulants (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo drastic adaptations to contribute to the enduring remodeling of excitatory synapses and to usually suppress drug seeking behavior. As a result, a loss-of-function mutation (knockout) of individual group III receptor subtypes often promotes drug seeking. This review summarizes the data from recent studies on three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and analyzes their roles in the regulation of dopamine and glutamate signaling in the striatum and their participation in the addictive properties of three major classes of drugs (psychostimulants, alcohol, and opiates).

KW - alcohol

KW - amphetamine

KW - cocaine

KW - group III metabotropic glutamate receptors

KW - opiate

UR - http://www.scopus.com/inward/record.url?scp=84890447521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890447521&partnerID=8YFLogxK

U2 - 10.1007/s11684-013-0291-1

DO - 10.1007/s11684-013-0291-1

M3 - Review article

VL - 7

SP - 445

EP - 451

JO - Frontiers of Medicine

JF - Frontiers of Medicine

SN - 2095-0217

IS - 4

ER -