BEHAVIORAL INVOLVEMENT OF CENTRAL DOPAMINE D-1 AND D-2 RECEPTORS IN 4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE(MPTP)-LESIONED PARKINSONIAN CYNOMOLGUS MONKEYS

To clarify the roles of dopamine D-1 and D-2 receptors in behavioral s ymptoms of Parkinson's disease, antiparkinsonian effects of various do pamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned parkinsonian monkeys were investigated with regard to induct ion of hyperactivity such as excitability, irritability and aggressive ness. The non-selective dopamine agonist apomorphine ameliorated the p arkinsonism, but induced marked hyperactivity dose-dependently. Pretre atment with either the dopamine D-1 antagonist SCH 23390 or the dopami ne D-2 antagonist sulpiride markedly suppressed the apomorphine-induce d hyperactivity with slight attenuation of the antiparkinsonian effect s. Both the dopamine D-2-receptor agonist quinpirole and the dopamine D-1-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose- dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 au gmented the antiparkinsonian effects without a marked induction of hyp eractivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effect s. These results suggest that stimulation of either central dopamine D -1 or D-2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D-1 and D-2 rec eptors causes marked hyperactivity which may be predictive of dopamine rgic psychiatric side effects.