Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice

Hippocampal neurogenesis can be regulated by extrinsic factors, such as exercise and antidepressants. While there is evidence that the selective serotonin reuptake inhibitor (SSRI) fluoxetine enhances neurogenesis, the new dual serotonergic-noradrenergic reuptake inhibitor (SNRI) duloxetine has not been evaluated in this context. In addition, it is unclear whether effects of antidepressants and running on cell genesis and behavior are of similar magnitude in mice. Here, we assessed neurogenesis and open-field behavior in 2-month-old female C57Bl/6 mice after 28 days of treatment with either fluoxetine (18 mg/kg), duloxetine (2, 6 or 18 mg/kg) or exercise. New cell survival, as measured by 5-bromo-2′-deoxyuridine (BrdU)-labeled cells, was enhanced by 200% in the running group only. Both running and fluoxetine, but not duloxetine, increased the percentage of new cells that became neurons. In the open-field test, animals treated with either drug spent less time in the center than controls and runners. In addition, fluoxetine treatment resulted in reduced locomotor activity. Together, these data show that the neurogenic response to exercise is much stronger than to antidepressants and imply a low likelihood that anxiolytic effects of these drugs are mediated by adult neurogenesis in C57Bl/6 mice.