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Dopaminergic mechanisms in hemiparkinsonian monkeys

From the Experimental Therapeutics Branch and Intramural Research Program, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD.

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, LY171555, 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.

Address correspondence and reprint requests to Dr. Chase, Experimental Therapeutics Branch, NINCDS, Building 10, Room 5C103, Bethesda, MD 20892.

Presented in part at the thirty-eighth annual meeting of the American Academy of Neurology, New Orleans, LA, April 1986.

Received September 22, 1986. Accepted for publication in final form January 14, 1987.

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