Symptomatic and asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates: biochemical changes in striatal regions.
Administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to primates produces an excellent behavioral model of idiopathic Parkinson's disease. In the vervet monkey, regional biochemical differences in the striatum of two 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups were examined one to two months after treatment and compared with controls; one group displayed no observable gross motor abnormalities after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (asymptomatic), whereas the other group became markedly parkinsonian (symptomatic). In both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups massive depletions of dopamine and homovanillic acid concentrations were observed in the striatum; generally, dopamine losses in the symptomatic group (greater than 95%) were greater than in the asymptomatic group (greater than 75%). However, in striatum, a marked heterogeneity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine susceptibility was found; certain striatal regions having 99% depletion of dopamine even in asymptomatic monkeys. Overall, in ventromedial regions of striatum the losses of dopamine and homovanillic acid concentrations were less than in dorsolateral regions at the same coronal level. There was a significant negative correlation between control homovanillic acid/dopamine ratios and susceptibility of examined regions to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Unlike idiopathic, but similar to postencephalitic, Parkinson's disease, dopamine and homovanillic acid levels in caudate nucleus were not spared relative to putamen; in fact, in the asymptomatic group caudate nucleus dopamine and homovanillic acid concentrations were depleted to a greater extent than in putamen.(ABSTRACT TRUNCATED AT 250 WORDS)
Elsworth
J D
JD
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Deutch
A Y
AY
Redmond
D E
DE
Taylor
J R
JR
Sladek
J R
JR
Roth
R H
RH
D000818:Animals; D002521:Cercopithecus; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*
D004298:Dopamine; D006719:Homovanillic Acid