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Corticotropin‐releasing factor receptor type 1 mediates stress‐induced relapse to opiate dependence in rats

The possible effect of different corticotropin-releasing factor receptor (CRFR) antagonists (α-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 μg α-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 μg α-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 μg α-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.