Tolerance to d-amphetamine and lack of cross-tolerance to other drugs in rats under a multiple schedule of food presentation.

Rats were trained under a multiple fixed-ratio 30-response, fixed-interval 5-min schedule of food presentation. Dose-response curves for d-amphetamine, pentobarbital, chlordiazepoxide, ethanol, morphine, phencyclidine and delta 9-tetrahydrocannabinol were determined. At low doses, pentobarbital and chlordiazepoxide produced small increases in response rates, whereas other drugs had no effect. At high doses, all drugs produced decreases in both fixed-ratio and fixed-interval rates of responding. With the exception of ethanol, all drugs produced decreases in fixed-ratio rates at lower doses than those which decreased fixed-interval rates. After the initial dose-response determinations, all animals received a single daily dose of d-amphetamine (10 mg/kg) after the behavioral session for 112 d-amphetamine (10 mg/kg) after the behavioral session for 112 consecutive days. Chronic postsession treatment with d-amphetamine produced a progressive decrease in rate of responding. Dose-response curves for all the drugs were redetermined after 2 weeks of chronic d-amphetamine treatment. During chronic d-amphetamine treatment, there was tolerance to the rate-decreasing effects of d-amphetamine. No cross-tolerance was observed for the other drugs tested.