Administration of paroxetine during pregnancy affects behavioral changes and hippocampal cell proliferation in male offspring in rats

Abstract

Background: Although the use of antidepressants during pregnancy has increased over the last several decades, their safety has remained a topic of debate. Selective serotonin reuptake inhibitors (SSRIs) can cross the placenta and affect perinatal outcomes in infants exposed during pregnancy. Recent studies suggest new risks for not only for structural malformations, but also long-term behavioral, developmental, and emotional disorders in offspring. Aim: We aimed to elucidate the effects by which in utero paroxetine exposure may affect the behavior and hippocampus of the offspring of paroxetine-treated rodent mothers. Methods: Paroxetine was administered daily to pregnant female Wistar rats from embryonic day (ED) 12.5 to ED 21 with oral sondes. Paroxetine 1 mg/kg/day or paroxetine 2.5 mg/kg/day or saline was given to the control group. We evaluated spontaneous locomotor activity, spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze (EPM) in male offspring at postnatal day 30. Bromodeoxyuridine (BrdU)-positive cells in the hippocampus were counted using a fluorescence microscope. Results: Locomotor activities significantly increased in the paroxetine 2.5 mg compared with the control group. The paroxetine 2.5 mg group spent less time in the closed arm than did the control and paroxetine 1 mg groups in the EPM. The number of BrdU-positive cells in the dentate gyrus was significantly increased in the paroxetine 2.5 mg compared with the control group. Conclusions: These findings suggest that oral administration of paroxetine during pregnancy induces hyperactivity, decreases anxiety, and increases cell proliferation in the hippocampus of male offspring.