New amphibian models for the study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Abstract

We report the development of two animal models in amphibians (frogs and salamanders) in whom 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces the behavioral (neurological) and biochemical equivalents of the human disease and, in addition, a measurable modification in at least one form of pigment-bearing cell from the neural crest, the skin melanocyte. We propose that this new approach can become an inexpensive, easily quantifiable model for the study of the effect of MPTP on the central and peripheral nervous systems. We also demonstrate that the toxic effect of MPTP can be completely abolished in vivo by treatment with a monoamine oxidase inhibitor and potentiated by an inhibitor of catechol-O-methyltransferase. MPTP is catabolised by oxidation into toxic metabolites, but 1-methyl-4-phenylpyridinium ion (MPP+), the proposed end-metabolite, is even more toxic than MPTP in this model, possibly through a different mechanism.