Effect of chronic intoxication with (+)-amphetamine on its concentration in liver and brain and on (14C) leucine incorporation into microsomal and cytoplasmic proteins of rat liver

Rats were treated with increasing concentrations of (+)-amphetamine sulphate in drinking water for 90 days. The ingested dose of amphetamine was found to increase from 16 mg kg^?1 on the first day up to 90 mg kg^?1 on the 32nd day of treatment. The rats were maintained on the highest dose regime for a further 58 days without any deaths, which showed that tolerance to the overall toxicity of the drug developed. The concentrations of ³H]amphetamine in liver and brain of chronically treated rats were significantly higher than those of controls. Chronic treatment with amphetamine significantly reduced body and liver weight of rats, but did not influence the relative liver to body weight. A marked inhibition of ¹⁴C]leucine incorporation into liver microsomal and cytoplasmic proteins was observed after 90 days of treatment with amphetamine. The relation between inhibition of microsomal protein synthesis and the increase of amphetamine concentrations in liver and brain is discussed.