Research article summary (published 27 Jul 2009):

Interoceptive effects of alcohol require mGlu5 receptor activity in the nucleus accumbens.

Full Abstract

The interoceptive effects of alcohol are major determinants of addiction liability. Metabotropic glutamate (mGlu) receptors are widely expressed in striatal circuits known to modulate drug-seeking. Given that the interoceptive effects of drugs can be important determinants of abuse liability, we hypothesized that striatal mGlu receptors modulate the interoceptive effects of alcohol. Using drug discrimination learning, rats were trained to discriminate alcohol (1 g/kg, i.g.) versus water. We found that systemic antagonism of metabotropic glutamate subtype 5 (mGlu5) receptors [10 mg/kg 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 3 mg/kg 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine], but not mGlu1 receptors ([0.3-3 mg/kg JNJ16259685) (3,4-dihydro-2H-pyrano[2,3]beta-quinolin-7-yl)(cis-4-methoxycyclohexyl) methanone)], inhibited the discriminative stimulus effects of alcohol. Furthermore, mGlu5 receptor antagonism (10 mg/kg MPEP) significantly inhibited neuronal activity in the nucleus accumbens core as levels of the transcription factor c-Fos were significantly reduced. Accordingly, targeted inhibition of mGlu5 receptors (20 microg of MPEP) in the nucleus accumbens core blunted the discriminative stimulus effects of alcohol (1 g/kg). Anatomical specificity was confirmed by the lack of effect of inhibition of mGlu5 receptors (10-30 microg of MPEP) in the dorsomedial caudate-putamen and the similar cytological expression patterns and relative density of mGlu5 receptors between the brain regions. Functional involvement of intra-accumbens mGlu5 receptors was confirmed as activation of mGlu5 receptors [10 microg of (RS)-2-amino-2-(2-chloro-5-hydroxyphenyl)acetic acid sodium salt] enhanced the discriminative stimulus effects of a low alcohol dose (0.5 g/kg), and mGlu5 receptor inhibition (20 microg of MPEP) prevented the agonist-induced enhancement. These results show that mGlu5 receptor activity in the nucleus accumbens is required for the expression of the interoceptive effects of alcohol.

Author information

Author/s: Besheer, Joyce (J); Grondin, Julie J M (JJ); Salling, Michael C (MC); Spanos, Marina (M); Stevenson, Rebekah A (RA); Hodge, Clyde W (CW);

Affiliation: Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. jbesheer(-atsign-)med.unc.edu

Grants: AA014983 (Agency:NIAAA NIH HHS) ; AA016009 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Jul; vol 29 (issue 30) : pp 9582-91

Dates: Created 2009/07/30; Completed 2009/08/19;

PMID: 19641121, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Caudate Nucleus - drug effects; metabolism Central Nervous System Depressants - pharmacology Conditioning, Operant - drug effects; physiology Discrimination Learning - drug effects; physiology Ethanol - pharmacology Male

Neurons - drug effects; metabolism Nucleus Accumbens - drug effects; metabolism Proto-Oncogene Proteins c-fos - metabolism Putamen - drug effects; metabolism Rats Rats, Long-Evans Receptors, Metabotropic Glutamate - antagonists & inhibitors; metabolism

Associated Chemicals: Central Nervous System Depressants (0) ; Proto-Oncogene Proteins c-fos (0) ; Receptors, Metabotropic Glutamate (0) ; metabotropic glutamate receptor 5 (0) ; metabotropic glutamate receptor type 1 (0) ; Ethanol (64-17-5)

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