CHANGES IN BRAIN DOPAMINE-RECEPTORS IN MPTP PARKINSONIAN MONKEYS FOLLOWING L-DOPA TREATMENT

Twenty-two monkeys (Macaca fascicularis) were utilized in this study. Ten animals were rendered parkinsonian with serial injections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Five of these parkinsonian monkeys received L-dopa/carbidopa treatment, and five animals did not. The remaining twelve animals did not receive MPTP. Eight of these animals received no L-dopa treatment, two animals were treated chronically with L-dopa/carbidopa and two animals received L-dopa/carbidopa only on the day of sacrifice. All animals were given weekly scored neurologic examinations throughout the study. Their movement was quantitated in an activity box. All animals were sacrificed by an overdose of sodium pentobarbital. The parkinsonian animals were sacrificed 107-355 days after their last MPTP injection. The brains were removed and frozen. Punch samples were taken from the caudate and putamen for tissue dopamine determination. Selected areas of the basal ganglia were cut into 20 mum sections for quantitative receptor autoradiography. The density of D1 and D2 receptors was evaluated in the basal ganglia of these animals at the level of the anterior commissure. For the D2 assay, total binding was determined using various concentrations of [H-3]spiperone in buffer containing 300 nm mianserine. For the D1 assay, total binding was determined using various concentrations of [H-3]SCH-23390. Tissue isotope concentration was determined from the autoradiographs. The MPTP parkinsonian monkeys showed a mean striatal dopamine depletion of 93.5% and a mean clinical score of 9.0. The untreated parkinsonian monkeys demonstrated an increase in the number of D2 sites as compared to controls. This increase was greatest in the lateral putamen. The L-dopa-treated parkinsonian monkeys demonstrated a decrease in the number of D2 sites below control levels. For the D1 sites, both the maximal number of binding sites and the affinity for SCH-23390 remained unchanged in all groups.