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Activation of group II metabotropic glutamate receptors attenuates both stress and cue-induced ethanol-seeking and modulates c-fos expression in the hippocampus and amygdala

Academic Article
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Overview

authors

  • Zhao, Y.
  • Dayas, C. V.
  • Aujla, H.
  • Baptista, M. A. S.
  • Martin-Fardon, Remi
  • Weiss, Friedbert

publication date

  • September 2006

journal

  • Journal of Neuroscience  Journal

abstract

  • Major precipitating factors for relapse to drug use are stress and exposure to drug-related environmental stimuli. Group II (mGlu(2/3)) metabotropic glutamate receptors (mGluRs) are densely expressed within circuitries mediating the motivating effects of stress and drug cues and, therefore, may participate in regulating drug-seeking linked to both of these risk factors. Thus, we tested the hypothesis that pharmacological activation of group II mGluRs modifies both stress- and cue-induced ethanol-seeking, using reinstatement models of relapse. In parallel, brain c-fos expression was examined to identify neural substrates for the behavioral effects of group II mGluR activation. The selective mGlu(2/3) agonist LY379268 (1R,4R,5S,6R-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate) (0.3, 1.0, and 3.0 mg/kg, s.c.) dose dependently blocked the recovery of extinguished ethanol-seeking induced by either footshock stress or ethanol-associated discriminative stimuli. These effects were accompanied by modulation of c-fos expression in the hippocampus, central nucleus of the amygdala, bed nucleus of the stria terminalis, and medial parvocellular paraventricular nucleus of the hypothalamus. The results implicate group II mGluRs as a shared neuropharmacological substrate for ethanol-seeking elicited by both drug cues and stress and identify group II mGluRs as promising treatment targets for relapse prevention.

subject areas

  • Alcohol Drinking
  • Alcoholism
  • Amino Acids
  • Amygdala
  • Animals
  • Anxiety
  • Bicyclo Compounds, Heterocyclic
  • Cues
  • Electroshock
  • Ethanol
  • Excitatory Amino Acid Agonists
  • Extinction, Psychological
  • Genes, fos
  • Hippocampus
  • Limbic System
  • Male
  • Motivation
  • Nerve Tissue Proteins
  • Paraventricular Hypothalamic Nucleus
  • Proto-Oncogene Proteins c-fos
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate
  • Reward
  • Secondary Prevention
  • Self Administration
  • Septal Nuclei
  • Stress, Physiological
  • Synaptic Transmission
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Research

keywords

  • addiction
  • alcohol
  • anxiolytic
  • glutamate
  • reinstatement
  • relapse
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.2384-06.2006

PubMed ID

  • 17005860
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Additional Document Info

start page

  • 9967

end page

  • 9974

volume

  • 26

issue

  • 39

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