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Intracarotid 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Administration: Biochemical and Behavioral Observations in a Primate Model of Hemiparkinsonism
Author(s) -
Guttman Mark,
Fibiger Hans C.,
Jakubovic Alexander,
Calne Donald B.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01966.x
Subject(s) - mptp , caudate nucleus , putamen , parkinsonism , nucleus accumbens , neurotoxin , dopamine , primate , striatum , lesion , chemistry , anesthesia , medicine , endocrinology , neuroscience , biology , pathology , dopaminergic , disease
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.