Chronic d-amphetamine or methamphetamine produces cross-tolerance to the discriminative and reinforcing stimulus effects of cocaine

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 277; no. 1; pp. 212 - 218
• Main Authors: Peltier, R L, Li, D H, Lytle, D, Taylor, C M, Emmett-Oglesby, M W
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.04.1996
• Subjects: Animals; Central Nervous System Stimulants - pharmacology; Cocaine - pharmacology; Dextroamphetamine - pharmacology; Discrimination Learning - drug effects; Dose-Response Relationship, Drug; Drug Tolerance; Male; Methamphetamine - pharmacology; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Reinforcement (Psychology); Self Administration
• ISSN: 0022-3565; 1521-0103

These experiments tested the hypothesis that chronic administration of d-amphetamine (d-A) or methamphetamine (METH) would produce cross-tolerance to the discriminative and/or reinforcing effects of cocaine. One group of rats (n = 20) was trained to detect cocaine (10.0 mg/kg; i.p.) from vehicle; cocaine (1.0-17.8 mg/kg) dose dependently substituted for the training dose. Chronic administration of d-A or METH (0.32, 1.0 and 3.2 mg/kg/12 hr for 7 days) resulted in cross-tolerance to the discriminative stimulus effects of cocaine. A second group of rats (n = 12) was implanted with indwelling jugular catheters and were trained to self-administer cocaine under a fixed-ratio 2 schedule of reinforcement. This group of rats also received chronic d-A or METH (0.32, 1.0 and 3.2 mg/kg/12 hr for 7 days. In this group, chronic administration of the highest dose of d-A and of METH (3.2 mg/kg) resulted in cross-tolerance to the self-administration of cocaine. A third group of rats (n = 15) was implanted with indwelling jugular catheters and were trained to self-administer cocaine under a progressive-ratio schedule of reinforcement. Chronic administration of d-A and METH (3.2 mg/kg/12 hr for 7 days) resulted in cross-tolerance to the self-administration of cocaine under this progressive-ratio schedule. The data obtained from these experiments demonstrate that chronic treatment with central nervous system stimulants of the amphetamine type (d-A or METH) produces cross-tolerance to both the discriminative and reinforcing effects of cocaine.