THE ROLE OF CORTICOTROPIN-RELEASING FACTOR AND CORTICOSTERONE IN STRESS-INDUCED AND COCAINE-INDUCED RELAPSE TO COCAINE SEEKING IN RATS

We have shown previously that footshock stress and priming injections of cocaine reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al., 1996). Here we examined the role of brain cortic otropin-releasing factor (CRF) and the adrenal hormone corticosterone in stress- and cocaine-induced reinstatement of cocaine seeking in rat s. The ability of footshock stress and priming injections of cocaine t o induce relapse to cocaine seeking was studied after intracerebrovent ricular infusions of the CRF receptor antagonist D-Phe CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone replacemen t. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion, i .v.) for 3 hr daily for 10-14 d and were then placed on an extinction schedule during which saline was substituted for cocaine. Tests for re instatement were given after intermittent footshock (10 min; 0.5 mA) a nd after priming injections of saline and cocaine (20 mg/kg, i.p.). Fo otshock reinstated cocaine seeking in both intact animals and animals with corticosterone replacement but not in adrenalectomized animals. T he CRF receptor antagonist D-Phe CRF12-41 blocked footshock-induced re instatement at all doses tested in both intact animals and animals wit h corticosterone replacement. Reinstatement by priming injections of c ocaine was only minimally attenuated by adrenalectomy and by pretreatm ent with D-Phe CRF12-41. These data suggest that brain CRF plays a cri tical role in stress-induced, but only a modulatory role in cocaine-in duced, reinstatement of cocaine seeking. Furthermore, the data show th at although reinstatement of cocaine seeking by footshock stress requi res minimal, basal, levels of corticosterone, stress-induced increases in corticosterone do not play a role in this effect.