Ths J0WIHAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTIC8 Copyright 01985 by The American Society for Pharmacology and Experimental Therapeutics Role of Dopamine in the Neurotoxic Effects of

Multiple administrations of high doses of methamphetamine to rats cause long-term depression of both dopamine and serotonin synthesis. Coadministration of the catecholamine synthesis in-hibitor, a-methyl-p-tyrosine, antagonizes this effect of metham-phetamine on both neurotransmitter systems. However, when catecholamine synthesis was maintained by the administration of L-dopa and the peripheral decarboxylase inhibitor R04-4602, a-methyl-p-tyrosine no longer prevented the effects of metham-phetamine on either dopamine or serotonin synthesis. In addition, the administration of the specific dopamine uptake blocker, amfonelic acid, significantly attenuated the changes in the sero-tonin synthesizing enzyme, tryptophan hydroxylase, resulting from multiple high doses of methamphetamine. The ability of a single administration of methamphetamine to depress tryptopha