Dopaminergic mechanisms in hemiparkinsonian monkeys

The motor effects of direct agonists which act selectively on certain dopamine receptors were studied in monkeys rendered hemiparkinsonian by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The D-2 dopamine agonist, LY 171555, but not the D-1 agonist, SKF 38393, reduced parkinsonian signs and induced rotation away from the side of the nigral lesion. When administered together, SKF 38393 diminished the LY 171555-induced turning in a dose-dependent manner. A selective D-1 antagonist, SCH 23390, induced mild and brief rotation when administered alone. These results suggest that D-2 receptor stimulation is necessary to ameliorate parkinsonism, but that pharmacologic manipulation of both D-1 and D-2 receptors may be required for an optimal therapeutic response.