Behavioral and biochemical effect of chronic treatment with D-1 and/or D-2 dopamine agonists in MPTP monkeys.

Monkeys developed a severe parkinsonian syndrome after intravenous administration of (MPTP). L-DOPA/carbidopa (D-1 and D-2) or bromocriptine (D-2) treatment relieved the parkinsonian symptoms, whereas SKF 38393 (D-1) was ineffective. No dyskinesia was seen in monkeys receiving bromocriptine or SKF 38393 as opposed to the L-DOPA-treated animals, in which the dyskinetic response appeared to increased with time. MPTP induced a significant increase (25%, P less than 0.01) in the number of [3H]spiperone binding sites (Bmax) in the caudate nucleus and in putamen. The Bmax of spiperone binding in the L-DOPA-treated monkeys was on average 18% lower (P less than 0.01) than that of the animals treated with MPTP alone. The Bmax for the bromocriptine-treated group was 29% (P less than 0.01) less than that in the MPTP-treated group or 11% (P less than 0.05) less than that in the L-DOPA-treated monkeys. The SKF 38393 treatment induced a 23% (P less than 0.01) decrease in the Bmax as compared to that of animals treated with MPTP alone, and no significant change compared to the L-DOPA- or bromocriptine-treated animals. These results suggest that stimulation of D-1 and D-2 dopamine receptors can differently influence the mechanisms controlling dopamine agonist-induced dyskinesia in MPTP-treated monkeys.