Contrasting tissue factors predict heterogeneous striatal dopamine neurotoxicity after MPTP or methamphetamine treatment.

Treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or (+)-methamphetamine (METH) results in regionally heterogeneous patterns of dopaminergic depletion. The magnitude of the MPTP-induced dopamine (DA) depletion corresponds directly to the density of [3H]mazindol binding to DA transport sites, but not the DA concentration, in intact mouse striatal regions. In contrast, the extent of METH-induced DA depletion corresponds to the intact dopamine concentration, not the [3H]mazindol binding, in the same striatal regions. The findings provide a rationale for testing different hypotheses regarding the neurobiological substrates of mesostriatal injury in idiopathic Parkinson's disease (PD).