Abstract
In this paper, using an in vitro superfusion system, we examined in the rat corpus striatum (CS) the action of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and N-methylphenylpyridine (MPP+) on dopamine (DA) metabolism. MPTP, at at 10(-5) M and 10(-4) M, caused decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) output in a dose-dependent manner. In addition, at 10(-4) M, MPTP caused an increase in DA release from CS. On the other hand, at 10(-6) M and 10(-5) M, MPP+ exerted very potent and rapid inhibition on DOPAC output and stimulated DA release in a dose-dependent manner. Furthermore, pretreatment of MPP+ markedly potentiated K+-stimulated DA release from CS. From the present data, we propose that MPP+ (the active metabolite of MPTP) inhibits DA reuptake system and/or monoamine oxidase (MAO) activity, increases readily releasable pool of DA and stimulates DA release from dopaminergic terminals.
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