Developmental fluoxetine exposure facilitates sexual behavior in female offspring.

RATIONALE: A growing number of infants are being exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. SSRIs target the serotoninergic system and are a popular treatment for maternal mood disorders. Serotonin itself plays a key role in the sexual differentiation through its role in the development of the hypothalamic-pituitary-gonadal axis, and previous research has shown that developmental SSRI exposure has an effect on sexual behavior in male offspring. OBJECTIVES: Our aim was to determine the role of developmental exposure to a popular SSRI medication, fluoxetine, on sexual differentiation of the brain and behavior in female offspring using a rodent model of maternal adversity. METHODS: Stressed and non-stressed Sprague-Dawley rat dams were chronically treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1. Four groups of female offspring were used: (1) control + vehicle, (2) control + fluoxetine, (3) prenatal stress + vehicle, and (4) prenatal stress + fluoxetine. RESULTS: Primary results show that in adult female offspring, developmental fluoxetine exposure facilitates proceptive and receptive behaviors with a significant increase in the number of proceptive behaviors, a significant increase in the lordosis quotient, and a significant decrease in the rejection quotient. CONCLUSIONS: This research contributes in the understanding of the long-term impact developmental fluoxetine exposure on the hypothalamus-pituitary-gonadal (HPG) system in adult female offspring.

Developmental fluoxetine exposure and prenatal stress alter sexual differentiation of the brain and reproductive behavior in male rat offspring.

Depression during pregnancy and postpartum is a significant health problem and affects up to 20% of women. While selective serotonin reuptake inhibitor (SSRI) medications are the drug of choice for treatment of maternal depression, the combined effect of maternal depression and perinatal SSRI exposure on offspring development is poorly investigated. Our aim was to determine the role of exposure to fluoxetine during development on sexual behavior and sexually dimorphic brain structures in male offspring using a rodent model of maternal adversity. Sprague-Dawley rat dams were stressed during gestation and were chronically treated throughout lactation with either fluoxetine or vehicle beginning on postnatal day 1. Four groups of offspring were used: (1) Control+Vehicle, (2) Control+Fluoxetine, (3) Prenatal Stress+Vehicle, and (4) Prenatal Stress+Fluoxetine. We show here that developmental fluoxetine treatment decreases the anogenital distance in juvenile male offspring. In adult male offspring, maternal fluoxetine treatment results in a decrease in the number of intromissions, a longer latency to the first intromission, and a longer latency to the first ejaculation. Furthermore, developmental fluoxetine and/or prenatal stress decrease the area of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Prenatal stress, but not exposure to developmental fluoxetine, decreases the number of tyrosine hydroxylase (TH)-positive cells in anteroventral periventricular nucleus (AVPv) and the volume of the posterior bed nucleus of the stria terminalis (pBST) in male offspring. These results provide important evidence for the long-term impact of maternal adversity and maternal fluoxetine use on the development of primary endocrinology systems in juvenile and adult male offspring.