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

Abstract

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 CB(1) 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 CB(1) receptor antagonist, AM251 (0, 10, 100 or 200 µg, i.c.v.), before tests for reinstatement in response to CRF (0, 0.5 µg, 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 µg, i.c.v.) before tests for locomotion in response to CRF (0.5 µg, 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 CB(1) receptor transmission in the effects of CRF on cocaine-related behaviours.