Hemiparkinsonism in monkeys following unilateral common carotid artery infusion of MPTP. A study of behavior, biochemistry and histology

Abstract

After local surgical exposure, we administrated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) directly into the right common carotid artery of 5 rhesus monkeys. All the monkeys manifested akinesia, rigidity and postural tremor of the contralateral limbs, and spontaneous circling toward the MPTP treated side. These disturbances began to appear 3-4 days after injection, peaking at one month, and continued until the day of sacrifice. After treatment with madopar and apomorphine, marked improvements of the motor impairments appeared and a striking reversal of the direction of rotation away from the MPTP-treated side occurred in a dose-dependent manner. The ipsilateral neurotoxicity was confirmed biochemically by 99% reduction in the caudate-putamen dopamine levels and histologically by selective cell loss in the substantia nigra of the MPTP-treated side. It is concluded that this primate model of hemiparkinsonism is easy to reproduce and life is maintained with good health otherwise. So it may be more feasible for behavioral and pharmacological studies of Parkinson's disease.