Effects of CP-154,526 on responding during extinction from cocaine self-administration in rats

Conditioned cues associated with cocaine induce craving and relapse. Although the role of corticotropin releasing hormone (CRH) in stress- and cocaine-induced relapse has been reported, its involvement in cue-induced behavior has not been established. Using responding during extinction as a model of cue-induced craving, we tested the effects of a selective CRH1 receptor antagonist, CP-154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine). Rats were trained to respond on a multiple schedule of cocaine self-administration and food reinforcement. On extinction test days, saline was substituted for cocaine. Pretreatment with CP-154,526 (20 mg/kg, i.p.) decreased responding on the cocaine-associated lever during extinction, suggesting an involvement of CRH1 receptors in cue-induced craving.