The neurotoxin MPTP does not reproduce in the rhesus monkey the interregional pattern of striatal dopamine loss typical of human idiopathic Parkinson's disease.
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.
Pifl
C
C
Institute of Biochemical Pharmacology, University of Vienna, Austria.
Schingnitz
G
G
Hornykiewicz
O
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006719:Homovanillic Acid