Pharmacologic modulation of MPTP toxicity: MK 801 in prevention of dopaminergic cell death in monkeys and mice.

Systemic administration of l-methyl-4phenyl-l,2,3,6-tetrahydropyridine (MPTP) induces, in primates, a neurologic syndrome identical to Parkinson's disease. This corresponds to an extensive and quite selective destruction of the dopaminergic neurons in the substantia nigra pars compacta (SNc) and a dramatic decrease of the dopamine content in the caudate and putamen nuclei. We have previously reported that, in mice, an anatomic and biochemical lesion similar to that observed in monkeys can be obtained by combining MPTP treatment with acetaldehyde (ACE).l-jH ere, we verified similarities between these two models by studying whether excitatory amino acids are involved in the mechanism of MPTP toxicity. A recent report indicates that MK 801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, is able to prevent the neuronal damage induced in the rat (a species insensitive to MRP) by intranigd injection of MPP+, the toxic MPTP metab~liteI.n~ both mice and monkeys, we systemically administered MK 801 together with MPTP and evaluated the behavioral, biochemical, and histologic effects 7 days after treatment.