Intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration: biochemical and behavioral observations in a primate model of hemiparkinsonism.
Cynomolgus monkeys received intracarotid injections of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce a chronic unilateral model of parkinsonism. Extensive dopamine (DA) depletion was observed in the caudate nucleus and putamen on the side ipsilateral to the injection and this was associated with contralateral tremor, rigidity, and bradykinesia. A dose of 1.25 mg of MPTP caused ipsilateral DA loss of 99.4% in the caudate nucleus, 99.8% in the putamen, and 74.2% in the nucleus accumbens. A dose of 2.5 mg caused ipsilateral DA depletion of 99.3% in the caudate nucleus, 99.5% in putamen, and 90.1% in the nucleus accumbens. The unilateral aspect of the lesion was dose sensitive, with the 2.5-mg dose causing bilateral asymmetric DA depletion. Tissue concentrations of serotonin were not affected by the toxin. These findings confirm that intracarotid injection of MPTP may produce a useful primate model of hemiparkinsonism that can be associated with selective unilateral DA depletion when the appropriate dose of toxin is used.
Guttman
M
M
Belzgerg Laboratory of Clinical Neuroscience, University of British Columbia, Vancouver, Canada.
Fibiger
H C
HC
Jakubovic
A
A
Calne
D B
DB
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002339:Carotid Arteries; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007269:Injections, Intra-Arterial; D008252:Macaca fascicularis; D008297:Male; D009994:Osmolar Concentration; D010300:Parkinson Disease / Q000378:metabolism* / Q000523:psychology; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid