The histological effects of intracerebral injection or infusion of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (1-methyl-4-phenylpyridinium) in rat and mouse.

Bilateral infusion of MPTP into the substantia nigra, ventral tegmental area or putamen of the rat brain provoked accumulation of leucocytes, but the periphery of nigral lesions showed no significant nerve cell loss. Tyrosine hydroxylase labelling of dopaminergic perikarya showed a normal staining pattern. In contrast, MPP+ was more destructive. After one day there was local degeneration of neuronal and glial elements. After one month there was tissue necrosis and central cavitation, but, like MPTP, there was no evidence of selective nigral cell loss. Striatal injection of MPP+ also failed to produce retrograde nigral damage. It is concluded that the toxicity of MPP+ applied directly to the dopamine system is a consequence of a severe non-selective necrotic lesion.