Sensitivity changes to dopaminergic agents in fine moto control of rhesus monkeys after repeated methamphetamine administration

Abstract

Long-term behavioral and neurochemical effects of repeated methamphetamine (MA) administration were investigated in rhesus monkeys trained to perform a fine motor task requiring control of exerted force for a specific time. Rhesus monkeys were trained to extend their arms into a tube to press a lever with a force between 25 and 40 g for 5 sec in order to receive 1.5 ml of water. The effects of intramuscular administration of MA, apomorphine (APO) and haloperidol (HAL) on responding were compared before and after a 2-week period of repeated MA administration. During this period, MA was given in 4 divided doses starting at a total daily dose of 4 mg/kg/day and increasing to 40 mg/kg/day. Tolerance to MA, increased sensitivity to HAL and no consistent sensitivity change to APO were observed when dose-response functions were redetermined starting 1 month after the repeated MA administration. One month after these determinations were completed, the brains of the monkeys were analyzed for changes in monoamines. Significant depletions of dopamine in the caudate nucleus and serotonin in the frontal cortex were seen. It is hypothesized that the sensitivity changes to the drugs on performance were related to the dopamine depletion.