Altered sensitivity to d-methylamphetamine, apomorphine, and haloperidol in rhesus monkeys depleted of caudate dopamine by repeated administration of d-methylamphetamine.
The long-term neurochemical and behavioral effects of repeated d-methylamphetamine (d-MA) administration were investigated using four male rhesus monkeys trained to lever-press for food on a DRL-40s schedule of reinforcement. Dose-response curves for d-MA (0.0625-2.0 mg/kg), apomorphine (0.025-0.4 mg/kg), and haloperidol (0.005-0.04 mg/kg) on responding showed that repeated d-MA administration (0.5-16.0 mg/kg/day) decreased sensitivity to d-MA and to apomorphine but increased sensitivity to haloperidol. At 3-6 months after the last injection of d-MA, a 48.1% decrease in caudate dopamine (DA) was observed, with the frontal cortex, midbrain, and pons-medulla showing no significant change. A trend toward increasing concentrations of norepinephrine was noted in the same brain areas, but only in the frontal cortex did this change reach significance. Specific binding of 3H-spiroperidol to caudate membrane preparations was not changed, while the Vmax of the caudate DA re-uptake process declined 32%, with no change in Km. These results suggest that exposure of DA neurons in the caudate nucleus to high concentrations of d-MA can lead to nerve terminal degeneration.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D004361:Drug Tolerance; D006220:Haloperidol / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects; D013569:Synapses / Q000187:drug effects
D011954:Receptors, Dopamine; D008694:Methamphetamine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine