Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine reduces the release of [3H]dopamine from rat striatal slices.

The systemic administration of 1-methyl-4-phenyl-1,2,3-6-tetrahydropyridine (MPTP) is neurotoxic to cerebral dopaminergic neurones in several animals species and can cause parkinsonism in man. The mechanism of action may involve the oxidation of MPTP in the brain to a pyridinium species, 1-methyl-4-phenylpyridine (MPP+). Systemic administration of MPTP in rats leads to little permanent damage. However, the stimulable release of 3H-labelled stores of dopamine from the rat striatum is transiently reduced by MPTP administration, with a concomitant reduction in the striatal dopamine receptor complement. No changes in acetylcholine release or modulation by dopamine receptors of either transmitter could be measured. The transient changes in dopamine release may provide a valuable insight into the plasticity of the nervous system and its recovery from neurotoxic insult.