Related Experiment Videos
Dyskinesias elicited by methamphetamine: susceptibility of former methadone-consuming monkeys
Abstract:
Rhesus monkeys with a history of drinking methadone but currently drug-free and control monkeys with no drug history were injected with methamphetamine hydrochloride (2 to 5 milligrams per kilogram of body weight). In six of seven monkeys which had consumed methadone the lowest dose immediately elicited pronounced oral dyskinesias virtually identical to those of human tardive dyskinesia. The control monkeys did not exhibit oral dyskinesias even after prolonged treatment with the highest dose. The clincial implications may be related to the functioning of brain dopaminergic systems.
Insights
Rhesus monkeys with a history of methadone use developed oral dyskinesias after methamphetamine exposure. Control monkeys did not show these effects, suggesting a link to prior drug history and brain dopaminergic systems.
Area of Science:
- Neuroscience
- Pharmacology
- Primatology
Background:
- Methadone is an opioid agonist used to treat opioid use disorder.
- Methamphetamine is a potent central nervous system stimulant.
- Tardive dyskinesia is a neurological disorder characterized by involuntary movements.
Purpose of the Study:
- To investigate the effects of methamphetamine hydrochloride on rhesus monkeys with a history of methadone consumption.
- To compare the response to methamphetamine in drug-experienced versus drug-naive monkeys.
- To explore potential links between prior methadone use, methamphetamine-induced oral dyskinesias, and dopaminergic system function.
Main Methods:
- Rhesus monkeys with and without a history of methadone use were administered varying doses of methamphetamine hydrochloride (2-5 mg/kg).
- Observed and recorded behavioral responses, specifically focusing on oral dyskinetic movements.
- Compared the incidence and severity of oral dyskinesias between the methadone-experienced and control groups.
Main Results:
- Six out of seven methadone-experienced monkeys exhibited pronounced oral dyskinesias at the lowest methamphetamine dose.
- These induced dyskinesias were clinically similar to human tardive dyskinesia.
- Control monkeys did not develop oral dyskinesias, even with prolonged exposure to the highest methamphetamine dose.
Conclusions:
- Prior methadone exposure in rhesus monkeys primes the brain to develop methamphetamine-induced oral dyskinesias.
- The findings suggest a significant role for brain dopaminergic systems in mediating these drug-induced movement disorders.
- This model may offer insights into the neurobiological mechanisms underlying tardive dyskinesia and the long-term effects of opioid substitution therapy.