Fluoxetine reduces L-DOPA-derived extracellular DA in the 6-OHDA-lesioned rat striatum.
We investigated the effect of fluoxetine, a selective serotonin reuptake inhibitor (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% reduction in the cumulative amount of extracellular DA during 300 min following L-DOPA administration (50 mg/kg, i.p.; p < 0.01). This effect was antagonized by pretreatment with WAY-100635, a potent 5-HT1A antagonist, indicating that this effect of fluoxetine is due to its indirect 5-HT1A agonistic property. These results suggest that SSRIs may impair motor functions in patients with Parkinson's disease by reducing efflux of exogenous L-DOPA-derived DA.
Yamato
H
H
Department of Neurology, Institute of Neurological Diseases, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8216, Japan.
Kannari
K
K
Shen
H
H
Suda
T
T
Matsunaga
M
M
D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use*; D005110:Extracellular Space / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage*; D007980:Levodopa / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
D018663:Adrenergic Agents; D004295:Dihydroxyphenylalanine; D004298:Dopamine; D015259:Dopamine Agents; D005473:Fluoxetine; D007980:Levodopa; D017367:Selective Serotonin Reuptake Inhibitors; C001388:6-hydroxydopa