Corticotropin-releasing factor receptor type I mediates stress-induced relapse to opiate dependence in rats

Neuroreport. 2000 Aug 3;11(11):2373-8. doi: 10.1097/00001756-200008030-00008.


The possible effect of different corticotropin-releasing factor receptor (CRFR) antagonists (alpha-helical CRF, CP-154,526 and AS-30) on the maintenance and reactivation of morphine-conditioned place preference (CPP) induced by morphine or footshock stress, respectively, were investigated in rats. The results show that morphine-induced maintenance of CPP was not affected by pretreatment with any CRFR antagonists. However, morphine-induced the reactivation of CPP was significantly attenuated by pre-administration of 10 microg alpha-helical CRF (i.c.v.). The maintenance of morphine CPP could be induced by repeated footshock and this effect was significantly attenuated by pretreatment of 10 microg alpha-helical CRF (i.c.v.) and 10 mg CP-154,526 (i.p.). Furthermore, following a 28-day extinction of morphine CPP, a single footshock could again elicit the reactivation of place preference that was blocked by pretreatment with 10 microg alpha-helical CRF (i.c.v.) and 1 or 10 mg CP-154,526 (i.p.). The present study demonstrates that CRFR type 1, but not CRFR type 2, mediates the stress-induced maintenance and reactivation of morphine CPP. These findings suggest that CRFR type 1 antagonists might be of some value in the treatment and prevention of stress-induced relapse to drug dependence long after detoxification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Corticotropin-Releasing Hormone / metabolism
  • Corticotropin-Releasing Hormone / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • Electric Stimulation / adverse effects
  • Male
  • Morphine / pharmacology
  • Neuropsychological Tests
  • Opioid-Related Disorders / drug therapy
  • Opioid-Related Disorders / physiopathology*
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Secondary Prevention
  • Stress, Physiological / drug therapy
  • Stress, Physiological / physiopathology*


  • CP 154526
  • CRF receptor type 2
  • Pyrimidines
  • Pyrroles
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Morphine
  • Corticotropin-Releasing Hormone