Long-lasting effects of transient, perinatal fluoxetine exposure on cell proliferation in the dentate gyrus of mice

Abstract

In the adult mammalian brain, up-regulation of serotonin via the selective serotonin reuptake inhibitor fluoxetine increases hippocampal neurogenesis. However, research assessing the long-term effects of modulating serotonin during the developmental period on hippocampal neurogenesis, is sparse. Here we evaluated hippocampal neurogenesis early (postnatal day 12), and later in life (postnatal day 60), in the offspring of mouse dams that were administered fluoxetine in their drinking water from embryonic day 15 (E15) through postnatal day 12 (P12). Fluoxetine-exposed mice had significantly higher levels of neuronal proliferation at P12, and P60, despite cessation of fluoxetine on P12. These effects were limited to proliferation, as survival of postnatal-born hippocampal neurons was unaltered. Mice exposed to fluoxetine also showed significantly higher levels of cell death, suggesting that homeostatic mechanisms present within the hippocampus may limit integration of adult-born neurons into the existing neuronal network. These findings demonstrate modulation of serotonin during development may be sufficient to induce long-lasting changes in hippocampal neurogenesis.