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.