Effects of the CRH receptor antagonist CP-154,526 on intravenous cocaine self-administration in rats

The role for corticotropin-releasing hormone (CRH) receptors ors in the maintenance of intravenous cocaine self-administration in vats was investigated using the centrally active, small molecule CRH1 receptor antagonist CP-154,526. In these experiments, adult male Wistar vats were allowed alternating 15-min periods of access to food reinforcement and cocaine self-administration (0.125, 0.25 or 0.5 mg/kg/infusion) during daily 2-h sessions. A I-min timeout separated access to the two reinforces. Pretreatment with CP-154,526 produced dose-related decreases in cocaine self-administration without affecting food-reinforced responding suggesting a specific effect of the antagonist on cocaine-maintained behavior. Drug intake tons decreased across several doses of cocaine, with the dose-response curve for cocaine self-administration shifted downward and flattened, suggesting that CP-154,526 decreased cocaine reinforcement. Furthermore, responding on the cocaine lever following CP 154,526 pretreatment teas significantly suppressed, even during the first 15 min oft he session, a time wizen rats typically sample the cocaine lever during extinction, suggesting that CRH receptors may also be involved in some off he conditioned effects of cocaine as well. These data are discussed in terms of the role for CRH in the neurobehavioral effects of cocaine. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.