CORTICOTROPIN-RELEASING FACTOR, BUT NOT CORTICOSTERONE, IS INVOLVED IN STRESS-INDUCED RELAPSE TO HEROIN-SEEKING IN RATS

We showed previously that brief footshock stress and priming injection s of heroin reinstate heroin-seeking after prolonged drug-free periods . Here, we examined whether the adrenal hormone, corticosterone, and b rain corticotropin-releasing factor (CRF) were involved in such reinst atement. We tested the effects of adrenalectomy, chronic exposure to t he corticosterone synthesis inhibitor metyrapone (100 mg/kg, s.c., twi ce daily), acute exposure to metyrapone, acute intracerebroventricular injections of CRF (0.3 and 1.0 mu g), and intracerebroventricular inj ections of the CRF antagonist alpha-helical CRF (3 and 10 mu g) Rats w ere trained to self-administer heroin (100 mu g/kg/ infusion, i.v.) fo r 12-14 d. Extinction sessions were given for 4-8 d (saline substitute d for heroin). Tests for reinstatement were given after priming inject ions of saline and of heroin (0.25 mg/kg, s.c.), and after intermitten t footshock (15 or 30 min, 0.5 mA). Adrenalectomy (performed after tra ining) did not affect reinstatement by heroin but appeared to potentia te the reinstatement by footshock. Chronic exposure to metyrapone (fro m the beginning of extinction) or an acute injection of metyrapone (3 hr before testing) did not alter the reinstatement of heroin-seeking i nduced by footshock or heroin. Acute exposure to metyrapone alone pote ntly reinstated heroin-seeking. In addition, acute exposure to CRF rei nstated heroin-seeking, and the CRF antagonist ct-helical CRF attenuat ed stress-induced relapse. The effect of the CRF antagonist on reinsta tement by heroin was less consistent. These results suggest that CRF, a major brain peptide involved in stress, contributes to relapse to he roin-seeking induced by stressors.