Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in the mouse: relationships between monoamine oxidase, MPTP metabolism and neurotoxicity.

Mice treated with MPTP had a marked decrement in their neostriatal content of dopamine and its metabolites compared to controls and a severe loss of nerve cells in the zona compacta of the substantia nigra. Furthermore, neostriatal synaptosomal preparations from MPTP-treated mice had a greatly diminished capacity to take up 3H-dopamine compared to control. These biochemical and histological changes seen in MPTP-treated mice are similar to those observed in Parkinson patients. In mice treated with the specific MAO-B inhibitor deprenil prior to MPTP, these changes were not observed. It thus follows that deprenil is able to protect against the MPTP-induced dopaminergic neurotoxicity in mice. These data suggest a critical role for MAO-B in MPTP-induced neurotoxicity.