MPTP-INDUCED PARKINSONISM IN PRIMATES - PATTERN OF STRIATAL DOPAMINE LOSS FOLLOWING ACUTE AND CHRONIC ADMINISTRATION

We analyzed the effect of two different schedules of 1-methyl-4-phenyl -1,2,3,6-tetrahydropyridine (MPTP) treatment on dopaminergic systems i n the striatum of cynomolgus monkeys. Acute MPTP treatment produced a marked dopamine (DA) depletion, more severe in the caudate nucleus tha n in the putamen. Chronic MPTP induced a more pronounced reduction in DA levels, the putamen being slightly more affected than the caudate n ucleus, in accord with immunohistochemical findings that showed a high er loss of tyrosine-hydroxylase positive neurons in ventral subpopulat ions of the substantia nigra pars compacta. A striking increment in th e quotient DOPAC + HVA/DA was also,observed in chronically but not in acutely treated monkeys, especially in the putamen. In chronically tre ated animals there was a nearly complete loss of DA in all subdivision s of the putamen. In the caudate nucleus, a rostrocaudal gradient of D A depletion was found, with a greater decrease in DA concentration in the rostral parts, especially in the dorsolateral portions The pattern of striatal DA loss characteristic of Parkinson's disease can be repr oduced to a certain extent in MPTP-intoxicated primates.