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.
Matsubara
K
K
Department of Legal Medicine, Shimane Medical University, Izumo, Japan.
Idzu
T
T
Kobayashi
Y
Y
Gonda
T
T
Okunishi
H
H
Kimura
K
K
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D002243:Carbolines; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D013779:Tetrodotoxin; D003042:Cocaine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine