The neurotoxin MPTP does not reproduce in the rhesus monkey the interregional pattern of striatal dopamine loss typical of human idiopathic Parkinson's disease

Neurosci Lett. 1988 Oct 5;92(2):228-33. doi: 10.1016/0304-3940(88)90066-3.

Abstract

Using high-pressure liquid chromatography with electrochemical detection, we measured dopamine (DA) and homovanillic acid (HVA) in caudate nucleus, putamen and substantia nigra in 4 untreated rhesus monkeys and 4 monkeys with permanent parkinsonism produced by repeated injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; total dose: 2.1-6.45 mg/kg, i.m.). MPTP consistently produced a severe striatal and nigral loss of DA and HVA and an increase in the ratio 'HVA/DA'. In this respect, MPTP mimicked the changes found in human Parkinson's disease (PD). However, MPTP lowered the DA in caudate (-99.6%) to the same degree as in putamen (-99.5%). This is in contrast to idiopathic PD where the caudate is significantly less affected by DA loss (-84%) than the putamen (-98%). Thus, in our rhesus monkeys MPTP failed to reproduce the interregional caudate-putamen gradient characteristic of idiopathic PD. The DA pattern produced by MPTP was similar to the DA loss in caudate (-98%) and putamen (-99%) observed in patients with postencephalitic parkinsonism.

Publication types

  • Comparative Study

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Female
  • Homovanillic Acid / metabolism
  • Humans
  • Macaca mulatta
  • Male
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism*
  • Pyridines / pharmacology*
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*

Substances

  • Pyridines
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Homovanillic Acid