Reuptake of L-DOPA-derived extracellular dopamine in the striatum with dopaminergic denervation via serotonin transporters.
The aim of our present study was to determine whether exogenous L-DOPA-derived extracellular dopamine (DA) in the denervated striatum is taken up via serotonin (5-HT) transporters. Rats with dopaminergic denervation by 6-hydroxydopamine were injected with L-DOPA 50 mg/kg (i.p.) and extracellular DA levels in the denervated striatum were measured using in vivo microdialysis technique. During the experiments, fluoxetine, a selective serotonin reuptake inhibitor, was locally perfused into the striatum through the microdialysis probe. Cumulative amounts of L-DOPA-derived extracellular DA during 300 min were increased by fluoxetine dose-dependently (10 microM and 50 microM). These results suggest that reuptake of DA via 5-HT transporters plays an important role in the clearance of L-DOPA-derived DA from the extracellular space when dopaminergic neurons are extensively denervated.
Kannari
Kazuya
K
Department of Neurology, Hirosaki University School of Medicine, Hirosaki, Japan. kankazu@cc.hirosaki-u.ac.jp
Shen
Huo
H
Arai
Akira
A
Tomiyama
Masahiko
M
Baba
Masayuki
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D015259:Dopamine Agents; D005473:Fluoxetine; D006719:Homovanillic Acid; D007980:Levodopa; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors