Long-term behavioral changes in the rhesus monkey after multiple daily injections of d-methylamphetamine.

The effects of multiple daily injections of d-methylamphetamine on spaced lever-press responding were investigated in the rhesus monkey. Responding was measured after single injections of d-mehtylamphetamine (0.0625-1.0 mg/kg) both before and after the monkeys were maintained on a multiple daily d-methylamphetamine injection regimen in doses ranging from 0.5 to 16 mg/kg/day. Tolerance developed to the suppressant effects of this drug on responding. As evidenced by a shift in the dose-response curve measuring number of responses and number of reinforcements per session, this tolerance persisted for at least three months after cessation of the multiple drug injection regimen. In order for tolerance to develop, it was necessary for the animals to perform the task while maintained on drug. When saline was substituted for d-methylamphetamine, no evidence of a withdrawal syndrome was seen.