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

Psychopharmacology (Berl). 2000 Jun;150(3):317-24. doi: 10.1007/s002130000411.


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. METHDOS: 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 microg; 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Alcoholism / psychology*
  • Animals
  • Corticosterone / pharmacology
  • Corticotropin-Releasing Hormone / physiology*
  • Electroshock
  • Extinction, Psychological / drug effects
  • Injections, Intraventricular
  • Male
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • Rats
  • Rats, Wistar
  • Recurrence
  • Self Administration
  • Stress, Psychological / psychology*


  • CP 154526
  • Pyrimidines
  • Pyrroles
  • Corticotropin-Releasing Hormone
  • Corticosterone