Fluoxetine does not affect the ischemia-induced increase of neurogenesis in the adult rat dentate gyrus

Ischemic insult enhances the proliferation of precursor cells in the dentate subgranular zone. This study was performed to determine whether fluoxetine further promotes the neurogenesis induced by transient forebrain ischemia in the rat dentate gyrus. Transient forebrain ischemia was induced by four-vessel occlusion for 10 min. First, to investigate whether the short-term treatment of fluoxetine influences ischemia-induced cell proliferation, rats were administered fluoxetine (5 mg/kg, i.p.) or a vehicle on days three to nine post-ischemia, and 5-bromo-2′-deoxyuridine-5′-monophosphate (BrdU, 75 mg/kg, i.p.) one hour after the last fluoxetine injection. On examination one day later, the number of BrdU-labeled cells was not significantly different between the fluoxetine- and vehicle-treated groups. Second, to identify whether the chronic treatment of fluoxetine has an effect on the survival of ischemia-induced newborn cells, rats were administered fluoxetine or a vehicle on days 3 to 23 post-ischemia, and BrdU (75 mg/kg, three times) nine days post-ischemia. On examination four weeks after the BrdU injection, the number of BrdU-labeled cells was not significantly different between the fluoxetineand vehicle-treated groups. Also, the rate of neuronal maturation was not significantly different between the two groups. These results show that fluoxetine does not affect the ischemiainduced increase of neurogenesis in the dentate gyrus of the adult rat.