MPTP-induced parkinsonism in primates: pattern of striatal dopamine loss following acute and chronic administration

Neurosci Lett. 1994 Jul 4;175(1-2):121-5. doi: 10.1016/0304-3940(94)91094-4.


We analyzed the effect of two different schedules of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment on dopaminergic systems in the striatum of cynomolgus monkeys. Acute MPTP treatment produced a marked dopamine (DA) depletion, more severe in the caudate nucleus than in the putamen. Chronic MPTP induced a more pronounced reduction in DA levels, the putamen being slightly more affected than the caudate nucleus, in accord with immunohistochemical findings that showed a higher loss of tyrosine-hydroxylase positive neurons in ventral subpopulations of the substantia nigra pars compacta. A striking increment in the quotient DOPAC+HVA/DA was also observed in chronically but not in acutely treated monkeys, especially in the putamen. In chronically treated animals there was a nearly complete loss of DA in all subdivisions of the putamen. In the caudate nucleus, a rostrocaudal gradient of DA 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 reproduced to a certain extent in MPTP-intoxicated primates.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage*
  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Drug Administration Schedule
  • Female
  • Homovanillic Acid / metabolism
  • MPTP Poisoning
  • Macaca fascicularis
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism


  • 3,4-Dihydroxyphenylacetic Acid
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Dopamine
  • Homovanillic Acid