Susceptibility to amphetamine-elicited dyskinesias following chronic methadone treatment in monkeys.

Eight rhesus monkeys that had drunk subdependence-producing doses of methadone daily for 10-22 months, and had subsequently been drug-free for 2-17 months, were injected with low doses of methamphetamine (MA). They immediately exhibited oral dyskinesias resembling the symptoms of tardive dyskinesia in humans, a condition resulting from chronic blockade of striatal dopamine receptors by neuroleptics. Eleven control monkeys failed to develop dyskinesias during prolonged MA administration. Control monkeys then received parenteral methadone, chlorpromazine, haloperidol, or saline for 45 days. Upon subsequent retest with MA, the methadone and chlorpromazine monkeys immediately displayed oral dyskinesias. Dopaminergic antagonists blocked MA-elicited dyskinesis, whereas neither a noradrenergic blocker nor sedative doses of phenobarbital and diazepam had any effect on dyskinesias. We suggest that receptor supersensitivity is produced by chronic treatment with methadone or other dopamine receptor blockers. Following treatment, stimulation of hypersensitive striatal receptors by the dopamine released by MA results in oral dyskinesias. The clinical implications for methadone maintenance treatment program patients are discussed.