Effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its metabolite, N-methyl-4-phenylpyridinium ion, on dopaminergic nigrostriatal neurons in the mouse.

A single subcutaneous injection in the C57 black mouse of 40 mg/kg of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a 90% depletion of striatal dopamine, as well as loss of 33% of neuronal cell bodies in the substantia nigra, zona compacta. By 4.5 months, there appears to be partial recovery of striatal dopaminergic function. After injection into mice, the MPTP metabolite, N-methyl-4-phenylpyridinium ion (MPP+) enters the striatum, and through some unknown mechanism is even more toxic than MPTP. However, repeated injections of maximally tolerated amounts of MPP+ do not damage dopaminergic nigrostriatal neurons.