Faculty Collaboration Database

Ketoconazole does not block cocaine discrimination or the cocaine-induced reinstatement of cocaine-seeking behavior. Pharmacol Biochem Behav 1999 Sep;64(1):65-73

Date

09/24/1999

Pubmed ID

10494999

DOI

10.1016/s0091-3057(99)00090-8

Scopus ID

2-s2.0-0032835215 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

Ketoconazole is an FDA-approved antifungal agent that also blocks the synthesis of adrenocorticosteroids and functions as a glucocorticoid receptor antagonist. It has been previously demonstrated that this drug blocks the stress-induced reinstatement of cocaine-seeking behavior and reduces low-dose cocaine self-administration in rats. In the present experiments, the effects of ketoconazole on the cocaine-induced reinstatement of extinguished cocaine-seeking behavior and on cocaine discrimination were investigated in male Wistar rats. In rats trained to self-administer cocaine (0.5 mg/kg/infusion) by pressing a lever under a fixed-ratio 4 schedule of reinforcement, cocaine (5-20 mg/kg, IP) dose dependently reinstated cocaine-seeking behavior following at least 10 days of extinction, during which responding on the cocaine lever resulted in no programmed consequences. Ketoconazole (50 mg/kg, IP) failed to block cocaine-induced reinstatement despite blocking cocaine-induced increases in plasma corticosterone. Ketoconazole (25 or 50 mg/kg) also failed to block cocaine discrimination in rats trained to discriminate 10 mg/kg cocaine from saline. In these rats, generalization to the training dose of cocaine was observed in the absence of increases in plasma corticosterone. The results of these experiments indicate that corticosterone may mediate the effects of stressors on cocaine-seeking behavior but not the direct effects of cocaine itself.

Author List

Mantsch JR, Goeders NE

Author

John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antifungal Agents
Catheterization
Cocaine
Cocaine-Related Disorders
Corticosterone
Dopamine Uptake Inhibitors
Electroshock
Extinction, Psychological
Ketoconazole
Male
Rats
Rats, Wistar