BEHAVIORAL INVOLVEMENT OF CENTRAL DOPAMINE D-1 AND D-2 RECEPTORS IN 1-METHYL-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 symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D-1 antagonist SCH 23390 or the dopamine D-2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. 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 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. 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 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.