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Susceptibility to amphetamine-elicited dyskinesias following chronic methadone treatment in monkeys
Abstract:
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.
Insights
Methadone treatment may lead to methamphetamine-induced oral dyskinesias in rhesus monkeys. This suggests potential neurological risks for patients in methadone maintenance programs.
Area of Science:
- Neuroscience
- Pharmacology
- Primate Research
Background:
- Chronic methadone use can alter dopamine receptor sensitivity.
- Oral dyskinesias are involuntary movements associated with neurological conditions.
Purpose of the Study:
- To investigate the long-term effects of methadone on dopamine receptor sensitivity.
- To determine if prior methadone exposure primes rhesus monkeys to develop oral dyskinesias upon methamphetamine administration.
Main Methods:
- Rhesus monkeys with prior methadone exposure were injected with methamphetamine.
- Control monkeys received various drug treatments or saline.
- Subsequent methamphetamine challenges were used to assess dyskinesia development.
Main Results:
- Monkeys with prior methadone exposure developed oral dyskinesias after methamphetamine injection.
- Control monkeys did not develop dyskinesias.
- Dopaminergic antagonists prevented methamphetamine-induced dyskinesias.
Conclusions:
- Chronic methadone treatment may induce dopamine receptor supersensitivity.
- This supersensitivity can lead to oral dyskinesias when dopamine levels are increased by methamphetamine.
- Findings have implications for patients in methadone maintenance programs.