Stress hormone exposure reduces mglur5 expression in the nucleus accumbens: Functional implications for interoceptive sensitivity to alcohol

Joyce Besheer, Kristen R. Fisher, Anel A. Jaramillo, Suzanne Frisbee, Reginald Cannady

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Escalations in alcohol drinking associated with experiencing stressful life events and chronic life stressors may be related to altered sensitivity to the interoceptive/subjective effects of alcohol. Indeed, through the use of drug discrimination methods, rats show decreased sensitivity to the discriminative stimulus (interoceptive) effects of alcohol following exposure to the stress hormone corticosterone (CORT). This exposure produces heightened elevations in plasma CORT levels (eg, as may be experienced by an individual during stressful episodes). We hypothesized that decreased sensitivity to alcohol may be related, in part, to changes in metabotropic glutamate receptors-subtype 5 (mGluR5) in the nucleus accumbens, as these receptors in this brain region are known to regulate the discriminative stimulus effects of alcohol. In the accumbens, we found reduced mGluR5 expression (immunohistochemistry and Western blot) and decreased neural activation (as measured by c-Fos immunohistochemistry) in response to a moderate alcohol dose (1 g/kg) following CORT exposure (7 days). The functional role of these CORT-induced adaptations in relation to the discriminative stimulus effects of alcohol was confirmed, as both the systemic administration of 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) an mGluR5 positive allosteric modulator and the intra-accumbens administration of (R,S)-2-Amino-2-(2-chloro-5-hydroxyphenyl)acetic acid sodium salt (CHPG) an mGluR5 agonist restored sensitivity to alcohol in discrimination-trained rats. These results suggest that activation of mGluR5 may alleviate the functional impact of the CORT-induced downregulation of mGluR5 in relation to sensitivity to alcohol. Understanding the contribution of such neuroadaptations to the interoceptive effects of alcohol may enrich our understanding of potential changes in subjective sensitivity to alcohol during stressful episodes.

Original languageEnglish
Pages (from-to)2376-2386
Number of pages11
Issue number10
StatePublished - Sep 2014

Bibliographical note

Funding Information:
This work was supported, in part, by funds from the National Institutes of Health AA019682 (JB), AA020914 (JB), ABMRF/The Foundation for Alcohol Research (JB), and by the Bowles Center for Alcohol Studies. The authors declare no conflict of interest.

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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