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-Me2NH+), on extracellular dopamine were studied in the striatum of freely moving rats. Perfusion of either 2,9-Me2NH+ or MPP+ through a microdialysis probe evoked a marked and dose-dependent increase of dopamine levels. Tetrodotoxin and Ca(2+)-free medium prevented the increase in dopamine levels induced by 2,9-Me2NH+, but not that induced by MPP+. Cocaine, 3 microM, intensified the 2,9-Me2 NH(+)-induced increase in extracellular dopamine and slightly attenuated the MPP(+)-induced efflux. S(-)-3-(3-Hydroxy-phenyl)-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-Me2NH+, but not that by MPP+. These results suggested that 2,9-Me2NH+ was a potent dopamine reuptake blocker, whereas MPP+ acts as an amphetamine-like dopamine releaser rather than a reuptake inhibitor on the membrane transporter.