LONG-TERM EFFECTS OF MULTIPLE DOSES OF METHAMPHETAMINE ON NEOSTRIATAL TRYPTHOPHAN HYDROXYLASE, TYROSINE-HYDROXYLASE, CHOLINE-ACETYLTRANSFERASE AND GLUTAMATE-DECARBOXYLASE ACTIVITIES

The long-term effects of methamphetamine (15 mg/kg, s.c.) on neostriatal enzyme activity were measured in rats treated every 6 hours for 24 hours and subsequently monitored for periods up to 30 days following administration of the drug. Tyrosine hydroxylase was maximally decreased after the first day of drug treatment but the depression persisted throughout a 30-day period. Within 15 hours after methamphetamine treatment was initiated, trytophan hydroxylase was dramatically depressed to 17% of control and was still maximally depressed 7.5 days after the last dose of the drug. In contrast, neostriatal choline acetyltransferase and glutamate decarboxylase activities were not altered acutely nor chronically by methamphetamine administration. It would appear that the toxic effects of methamphetamine reported previously cannot be attributed to a generalized destruction of the neostriatum but are demonstrable only in selected biogenic amine nerve terminals. © 1979.