Changes in brain catecholamines and dopamine uptake sites at different stages of MPTP parkinsonism in monkeys

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to produce parkinsonism in primates. We have studied the changes in brain catecholamines and the distribution of desipramine insensitive mazindol binding sites in MPTP parkinsonian primates at different levels of parkinsonism. Thirty-seven monkeys (Macaca fascicularis) were utilized in this study. Twelve naive animals received no treatment and served as controls. Twenty-five animals were rendered parkinsonian with serial injections of MPTP. All animals were given scored neurologic examinations throughout the study. Their movement was quantitated in an activity box. The animals were sacrificed 30-360 days after their last MPTP injection. The clinical exam of the MPTP parkinsonian monkeys demonstrated mildly to severely affected animals. There was an exponential decrease in brain catecholamine levels with increased clinical parkinsonism. The MPTP parkinsonian animals showed the greatest decrease (67-99.8%) in tissue dopamine levels in the caudate nucleus. The putamen followed closely in severity (48-99.8%) and the nucleus accumbens was much less affected (0-40%). The percent reduction of norepinephrine in the anterior pole of the frontal cortex (0-48%) was similar in degree to the decreased dopamine levels in the nucleus accumbens. Mazindol binding was decreased 30-98% in the caudate nucleus, 20-97% in the putamen, 0-26% in the nucleus accumbens, 80-96% in the substantia nigra pars compacta and 49-94% in the ventral tegmental area. In the striatum, the decreased mazindol binding was more pronounced laterally and posteriorly. In each animal, there was good correlation between tissue dopamine levels and the number of mazindol binding sites.