Prenatal exposure to fluoxetine modulates emotionality and aversive memory in male and female rat offspring.

During pregnancy, women are prone to depression, for which selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are usually the first-line treatment. However, fluoxetine can cross the placental barrier and affect fetuses, causing changes in serotonin levels early in life. Long-term effects in the brain circuits that control cognitive and emotional behavior are related to early fluoxetine exposure during development. In this study, we aimed to investigate whether fluoxetine exposure (10 mg/kg/day) from the 13th gestational day (GD13) to GD21 may lead to behavioral emotional-cognitive changes in male and female rat offspring approximately 90 days postnatally (~PN90). We have analyzed the performance of individuals in the open field and in the plus-maze discriminative avoidance task, which assesses anxiety and learning/memory processing behaviors. We have found that prenatal (GD13-GD21) exposure to fluoxetine strengthened aversive memory and induced higher anxiety levels in males, and quick extinction of aversive memory in females. Taken together, these results suggest that early exposure to fluoxetine impairs the basal state of anxiety and the cognitive functions of rats during adulthood, which may be in a sex-specific manner because males appear more susceptible than females.