Long-term alterations in serotonin transporter expression after adolescent fluoxetine exposure: Insights from the...

Prescription rates of fluoxetine, the most dispensed selective serotonin reuptake inhibitor, have been rising among the juvenile population. Since adolescence is a critical developmental period in which the brain undergoes fine-tuning, chronic increases in serotonin levels may lead to long-term neurobiological changes in brain regions responsible for emotional regulation. Thus, using mice as a model system, we explored how adolescent fluoxetine exposure (AFE) would influence the expression of serotonin transporters (SERT) in the adult hippocampus and prefrontal cortex. Specifically, postnatal day (PD)-35 male C57BL/6 mice were administered with fluoxetine (250 mg/l in their drinking water) for 15 consecutive days (PD35-49). Three weeks later, when mice reached adulthood (PD70), bilateral hippocampus and prefrontal cortex were dissected and analyzed for SERT protein expression. We found that, when compared to controls, AFE-mice exhibited increased SERT protein expression in the hippocampus. In contrast, expression of SERTs was decreased in the prefrontal cortex of these mice. Our data suggest that AFE induces long-term region-specific changes in SERT expression. Collectively, this study demonstrates that persistent fluoxetine-induced neurobiological changes are evident in adulthood when exposed to this antidepressant medication during the adolescent stage of development.