Psychopharmacology

, Volume 150, Issue 3, pp 317–324

The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats

  • A. D. Lê
  • S. Harding
  • W. Juzytsch
  • J. Watchus
  • U. Shalev
  • Y. Shaham
Original Investigation

DOI: 10.1007/s002130000411

Cite this article as:
Lê, A., Harding, S., Juzytsch, W. et al. Psychopharmacology (2000) 150: 317. doi:10.1007/s002130000411

Abstract.

Rationale: Intermittent footshock stress reliably reinstates extinguished alcohol-taking behavior in drug-free rats, but the neurochemical events involved in this effect are not known. Objective: We studied here whether two main modulators of stress responses, corticotropin-releasing factor (CRF) and corticosterone, are involved in reinstatement of alcohol seeking induced by the intermittent footshock stressor. Methods: Rats were given alcohol in a two-bottle choice procedure (water versus alcohol) for 30 days and were then trained for 60 min per day to press a lever for alcohol (12% w/v) for 24–30 days in operant conditioning chambers. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 5–8 days. Reinstatement of alcohol seeking was then determined after exposure to intermittent footshock (0.8 mA; 10 min) in different groups of rats that were pretreated with CRF receptor antagonists or underwent adrenalectomy (ADX) to remove endogenous corticosterone from the body. Results: The CRF receptor antagonists, d-phe-CRF (0.3 or 1.0 µg; ICV) and CP-154,526 (15, 30 or 45 mg/kg; IP) attenuated footshock-induced reinstatement of alcohol seeking in a dose dependent manner. In contrast, the removal of circulating corticosterone by ADX had no effect on footshock stress-induced reinstatement of alcohol-taking behavior. In addition, the prevention of the footshock-induced rise in corticosterone while maintaining basal levels of the hormone by providing adrenalectomized rats with corticosterone pellets (50 mg/kg per day), had no effect on stress-induced reinstatement. Conclusions: These data suggest that CRF contributes to stress-induced relapse to alcohol seeking via its actions on extra-hypothalamic sites. The present data, and previous data with heroin- and cocaine-trained rats, point to a general role of CRF in relapse to drugs induced by stressors.

Adrenalectomy Alcohol Corticosterone Corticotropin-releasing factor Reinstatement – Relapse Stress

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • A. D. Lê
    • 1
  • S. Harding
    • 1
  • W. Juzytsch
    • 1
  • J. Watchus
    • 1
  • U. Shalev
    • 3
  • Y. Shaham
    • 3
  1. 1.Department of Neuroscience, Center for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada M5S 2S1Canada
  2. 2.Department of Pharmacology, University of Toronto, Toronto, CanadaCanada
  3. 3.Behavioral Neuroscience Branch, NIDA/IRP, Baltimore, Maryland, USAUSA