Localization in rat brain of binding sites for parkinsonian toxin MPTP: similarities with [3H]pargyline binding to monoamine oxidase.

A high-affinity binding site exists in rat brain for the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The pharmacological specificity of this binding site suggests that it may correspond to monoamine oxidase (MAO). We have used quantitative autoradiography to map in detail the anatomical distribution of the [3H]MPTP binding site in rat brain and compared it with the anatomical distribution of MAO as determined by in vitro autoradiography with [3H]pargyline. Under the conditions of the assay, [3H]pargyline labeled the type B form of MAO. There were strong similarities in the anatomical distribution of [3H]MPTP and [3H]pargyline, with high levels of both binding sites occurring in the arcuate nucleus, the locus coeruleus, the dorsal raphe nucleus and all circumventricular organs. Low levels of both binding sites were found in the substantia nigra and the caudate-putamen. These results provide additional evidence that the high-affinity binding site for MPTP is MAO. The parkinsonian actions of MPTP might result from metabolites produced by MAO.