Fluoxetine reduces L-DOPA-derived extracellular DA in the 6-OHDA-lesioned rat striatum?

We investigated the effect of fluoxetine, a selective serotonin reuptake in hibitor (SSRI), on L-DOPA-derived extracellular dopamine (DA) levels in the striatum of rats with nigrostriatal dopaminergic denervation using in vivo microdialysis. Treatment with fluoxetine (10 mg/kg, i.p.) induced a 41% re duction in the cumulative amount of extracellular DA during 300 min followi ng L-DOPA administration (50 mg/kg, i.p.; p < 0.01). This effect was antago nized by pretreatment with WAY-100635, a potent 5-HTIA antagonist, indicati ng that this effect of fluoxetine is due to its indirect 5-HTIA agonistic p roperty. These results suggest that SSRls may impair motor functions in pat ients with Parkinson's disease by reducing efflux of exogenous L-DOPA-deriv ed DA. NeuroReport 12:1123-1126 (C) 2001 Lippincott Williams & Wilkins.