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 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.
Department of Pharmacology, University of Navarra Medical School, Pamplona, Spain.
I
I
Pérez-Otaño
C
C
Oset
M R
MR
Luquin
M T
MT
Herrero
J A
JA
Obeso
J
J
Del Río
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid