Differences in dopamine efflux induced by MPP(+) and beta-carbolinium in the striatum of conscious rats

The effects of N-methyl-4-phenylpyridinium cation (MPP(+)) and of an endogenously formed analog, 2,9-di-methyl-norharmanium cation (2,9-Me(2)NH(+)), on extracellular dopamine were studied in the striatum of freely moving rats. Perfusion of either 2,9-Me(2)NH(+) or MPP(+) through a microdialysis probe evoked a marked and dose-dependent increase of dopamine levels. Tetrodotoxin and Ca2+-free medium prevented the increase in dopamine levels induced by 2,9-Me(2)NH(+), but not that induced by MPP(+). Cocaine, 3 mu M, intensified the 2,9-Me(2)NH(+)-induced increase in extracellular dopamine and slightly attenuated the MPP(+)-induced efflux. S(-)-3-(3-Hydroxyphenyl)-N-propylpiperidine, that acts as an antagonist of dopamine autoreceptors in the presence of a dopamine reuptake inhibitor, markedly enhanced the increase in extracellular dopamine elicited by 2,9-Me(2)NH(+), but not that by MPP(+). These results suggested that 2,9-Me(2)NH(+) was a potent dopamine reuptake blocker, whereas MPP(+) acts as an amphetamine-like dopamine releaser rather than a reuptake inhibitor on the membrane transporter.