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Pharmacologic Modulation of MPTP Toxicity: MK 801 in Prevention of Dopaminergic Cell Death in Monkeys and Mice
Author(s) -
ZUDDAS ALESSANDRO,
VAGLINI FRANCESCA,
FORNAI FRANCESCO,
FASCETTI FLAVIA,
SAGINARIO ANTONIO,
CORSINI GIOVANNI U.
Publication year - 1992
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1992.tb24553.x
Subject(s) - medicine , humanities , art
Systemic administration of l-methyl-4phenyl-l,2,3,6-tetrahydropyridine (MPTP) induces,\udin primates, a neurologic syndrome identical to Parkinson's disease. This corresponds\udto an extensive and quite selective destruction of the dopaminergic neurons\udin the substantia nigra pars compacta (SNc) and a dramatic decrease of the dopamine\udcontent in the caudate and putamen nuclei. We have previously reported that, in mice,\udan anatomic and biochemical lesion similar to that observed in monkeys can be obtained\udby combining MPTP treatment with acetaldehyde (ACE).l-jH ere, we verified\udsimilarities between these two models by studying whether excitatory amino acids are\udinvolved in the mechanism of MPTP toxicity. A recent report indicates that MK 801,\uda noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, is able\udto prevent the neuronal damage induced in the rat (a species insensitive to MRP) by\udintranigd injection of MPP+, the toxic MPTP metab~liteI.n~ both mice and monkeys,\udwe systemically administered MK 801 together with MPTP and evaluated the\udbehavioral, biochemical, and histologic effects 7 days after treatment