The effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the efflux and metabolism of endogenous dopamine in rat striatal slices.

1-Methyl-4-phenylpyridinium ion (MPP+) was shown to accumulate concentration-dependently in slices from rat striatum. At 10 microM, MPP+, the tissue concentration was found to be 118 +/- 9 microM following 75 min of incubation. The accumulation of MPP+ was reduced in the presence of 10 microM of the selective dopamine uptake inhibitor GBR 12909 (-50%) or by destruction of the dopaminergic terminals by complete hemisection of the forebrain 4 days before the experiments (-75%). Accumulation of MPP+ in the catecholamine-poor occipital cortex and cerebellum was only 25% of that obtained in striatum. Reserpine pretreatment of the rats in-vivo did not modify the accumulation of MPP+ in the striatal slices. MPP+ (1-10 microM) increased the net efflux of dopamine and reduced the efflux of the dopamine metabolite DOPAC from the striatal slices. The effect on dopamine was readily diminished if MPP+, after a 15 min incubation, was then omitted from the medium. In contrast, the DOPAC efflux was reduced for 75 min even though MPP+ was present in the incubation medium only for the first 15 min. In the presence of the monoamine oxidase inhibitor, pargyline (350 microM), MPP+ also produced an increase in dopamine efflux. In normal medium, the presence of the dopamine uptake inhibitor GBR 12909 (10 microM), or the absence of calcium, failed to modify the MPP+-induced increase in dopamine efflux. MPP+ also increased dopamine efflux from slices from reserpinized rats.(ABSTRACT TRUNCATED AT 250 WORDS)