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Additive effect of stress and drug cues on reinstatement of ethanol seeking: Exacerbation by history of dependence and role of concurrent activation of corticotropin-releasing factor and opioid mechanisms

Academic Article
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Overview

authors

  • Liu, X.
  • Weiss, Friedbert

publication date

  • September 2002

journal

  • Journal of Neuroscience  Journal

abstract

  • Stress and exposure to drug-related environmental stimuli have been implicated as critical factors in relapse to drug use. What has received little attention, however, is the significance of interactions between these factors for motivating drug-seeking behavior. To address this issue, a reinstatement model of relapse was used. Footshock stress and response-contingent presentation of an ethanol-associated light cue, acting as a conditioned stimulus (CS), effectively reinstated extinguished responding at a previously active, drug-paired lever in male Wistar rats. When response-contingent availability of the ethanol CS was preceded by footshock, additive effects of these stimuli on responding were observed. Both the individual and interactive effects of footshock and the CS were significantly greater in previously ethanol-dependent than in nondependent rats. Responding induced by the ethanol CS was selectively reversed by the nonselective opiate antagonist naltrexone, whereas the effects of footshock were selectively reversed by the corticotropin-releasing factor (CRF) antagonist d-Phe-CRF(12-41). However, both agents only partially reversed the enhanced drug-seeking response produced by the interactive effects of stress and the ethanol CS; full reversal required coadministration of d-Phe-CRF and naltrexone. The results document that stress and drug-related environmental stimuli interact to augment the resumption of drug seeking after extinction and suggest that this effect results from concurrent activation of opioid and CRF transmission.

subject areas

  • Administration, Inhalation
  • Alcoholism
  • Animals
  • Appetitive Behavior
  • Behavior, Animal
  • Conditioning (Psychology)
  • Corticotropin-Releasing Hormone
  • Cues
  • Disease Models, Animal
  • Drug Synergism
  • Electroshock
  • Ethanol
  • Male
  • Naltrexone
  • Narcotic Antagonists
  • Rats
  • Rats, Wistar
  • Receptors, Opioid
  • Recurrence
  • Self Administration
  • Stress, Physiological
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Research

keywords

  • D-Phe-CRF
  • conditioned stimulus
  • dependence
  • ethanol
  • footshock
  • naltrexone
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

PubMed ID

  • 12223538
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Additional Document Info

start page

  • 7856

end page

  • 7861

volume

  • 22

issue

  • 18

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