Format

Send to

Choose Destination
See comment in PubMed Commons below
Biol Psychiatry. 2009 Apr 15;65(8):717-20. doi: 10.1016/j.biopsych.2008.11.001. Epub 2008 Dec 19.

Positive allosteric modulation of mGluR5 receptors facilitates extinction of a cocaine contextual memory.

Author information

1
Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Abstract

BACKGROUND:

The perseverance of the motivational salience of drug-associated memories is an obstacle to the successful treatment of drug addiction and is often a causative factor in triggering relapse.

METHODS:

This study was intended to determine whether potentiation of type 5 metabotropic glutamate receptors (mGluR5), which are biochemically and structurally coupled to N-methyl-D-aspartate (NMDA) receptors, would facilitate the extinction of a cocaine-associated contextual memory as assessed by the conditioned place preference (CPP) paradigm in rats. Following the establishment of a cocaine CPP, rats were treated with the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB; 0.3, 3 and 30 mg/kg) before extinction test sessions. Additional groups of animals received 30 mg/kg CDPPB in combination with the mGluR5 antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP, 1 mg/kg) or the NMDA receptor antagonist MK-801 (.1 mg/kg).

RESULTS:

CDPPB dose-dependently facilitated the extinction of cocaine CPP, and these effects were not observed when animals were coadministered MTEP or MK-801. CDPPB failed to produce any evidence of neurotoxicity as assessed by FluoroJade C staining.

CONCLUSIONS:

Positive allosteric modulation of mGluR5 function facilitates the extinction of a cocaine-associated contextual memory, which may represent a novel approach toward enhancing extinction learning in the context of drug addiction.

PMID:
19100966
PMCID:
PMC2870714
DOI:
10.1016/j.biopsych.2008.11.001
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center