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Rats with extended access to cocaine exhibit increased stress reactivity and sensitivity to the anxiolytic-like effects of the mGluR 2/3 agonist LY379268 during abstinence

Academic Article
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Overview

authors

  • Aujla, H.
  • Martin-Fardon, Remi
  • Weiss, Friedbert

publication date

  • July 2008

journal

  • Neuropsychopharmacology  Journal

abstract

  • Metabotropic glutamate 2/3 receptors (mGluR2/3) are emerging targets for the reduction of stress that contributes to drug relapse. The effect of a history of cocaine escalation on stress reactivity during abstinence and the role of mGlu2/3 receptors in stress in these animals were tested. Experiment 1-Rats trained to self-administer cocaine, under short (ShA, 1-h) or long (LgA, 6-h) access conditions, or noncaloric food pellets (Ctrl, 1-h), were tested for stress reactivity in the shock-probe defensive burying test following 1, 14, 42, or 84 days of abstinence. Experiment 2-Experimentally naive rats receiving the mGlu2/3 receptor agonist LY379268 (0, 0.3, 1.0, or 3.0 mg/kg) were tested in the defensive burying test to establish the anxiolytic efficacy of this compound in this model. Experiment 3-Rats with a history of ShA vs LgA cocaine self-administration, or a history of operant responding reinforced by noncaloric food pellets, were tested in the defensive burying test, following administration of LY379268 (0.3, 1.0, or 3.0 mg/kg) at 14 days of abstinence. LgA rats exhibited a two- to threefold increase in defensive burying at 1, 14, and 42 days of abstinence compared to ShA or control animals. LY379268 (3.0 mg/kg) reduced burying in all groups, whereas the 1.0-mg/kg dose reduced burying only in the LgA group. A robust and enduring increase in stress reactivity developed in rats with a history of daily 6-h access to cocaine. The anxiolytic-like effects of LY379268 identify mGlu2/3 receptors as targets for ameliorating stress-associated relapse risk, and point toward the possibility that a history of cocaine escalation in rats may modify glutamatergic function.

subject areas

  • Amino Acids
  • Animals
  • Anti-Anxiety Agents
  • Bicyclo Compounds, Heterocyclic
  • Cocaine-Related Disorders
  • Dose-Response Relationship, Drug
  • Electroshock
  • Excitatory Amino Acid Agonists
  • Food
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate
  • Reinforcement (Psychology)
  • Stress, Psychological
  • Substance Withdrawal Syndrome
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Research

keywords

  • abstinence
  • cocaine
  • defensive burying
  • escalation
  • metabotropic glutamate
  • stress
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Identity

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/sj.npp.1301588

PubMed ID

  • 17895914
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Additional Document Info

start page

  • 1818

end page

  • 1826

volume

  • 33

issue

  • 8

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