Positive Allosteric Modulation of mGluR5 Receptors Facilitates Extinction of a Cocaine Contextual Memory

Justin T. Gass, M. Foster Olive

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)717-720
Number of pages4
JournalBiological Psychiatry
Volume65
Issue number8
DOIs
StatePublished - Apr 15 2009

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Keywords

  • Cocaine
  • conditioned place preference
  • contextual memory
  • extinction learning
  • mGluR5

ASJC Scopus subject areas

  • Biological Psychiatry

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