Cannabinoid CB1 receptors mediate the effects of corticotropin-releasing factor on the reinstatement of cocaine seeking and expression of cocaine-induced behavioural sensitization

BACKGROUND AND PURPOSE The endocannabinoid and corticotropin-releasing factor (CRF) systems have been implicated in several long-lasting behavioural effects of prior cocaine experience. The present experiments were designed to probe functional interactions between endocannabinoids and CRF by testing the role of cannabinoid CB1 receptors in cocaine-related behaviours induced or mediated by CRF. EXPERIMENTAL APPROACH In Experiment 1, rats trained to self-administer cocaine were pretreated with the CB1 receptor antagonist, AM251 (0, 10, 100 or 200 mu g, i. c. v.), before tests for reinstatement in response to CRF (0, 0.5 mu g, i. c. v.), intermittent footshock stress (0, 0.9 mA) or cocaine (0, 10 mg.kg(-1), i. p.). In Experiment 2, rats pre-exposed to cocaine (15-30 mg.kg(-1), i. p.) or saline for 7 days were pretreated with AM251 (0, 10 or 100 mu g, i. c. v.) before tests for locomotion in response to CRF (0.5 mu g, i. c. v.), cocaine (15 mg.kg(-1), i. p.) or saline (i. c. v.). KEY RESULTS Pretreatment with AM251 selectively interfered with CRF-, but not footshock- or cocaine-induced reinstatement. AM251 blocked the expression of behavioural sensitization induced by challenge injections of both CRF and cocaine. CONCLUSIONS AND IMPLICATIONS These findings reveal a mediating role for CB1 receptor transmission in the effects of CRF on cocaine-related behaviours.