Regional and temporal effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine uptake sites in mouse brain

When the regional effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopamine uptake sites in C57 Black mice were studied using [3H]mazindol autoradiography, marked regional differences in effect were seen: the mesolimbic system was less affected than the nigrostriatal tract and within each system the effect was more severe in the terminal fields of the striatum than in the cells of origin. Within the striatum itself there was inhomogeneity of effect, with relative sparing of the dorsomedial aspect compared to the remainder. Complete recovery of [3H]mazindol binding to striatal membranes occurred over 12 months, while dopamine levels recovered more slowly. This supports the concept that MPTP has a highly selective effect within dopaminergic systems and that the initial effect is more pronounced on distal terminals compared to cell bodies. The possibility that recovery of mazindol binding with time may be associated with terminal regrowth needs to be investigated further.