ADMINISTRATION OF SSRI DURING PREGNANCY AFFECTED BEHAVIORAL CHANGES AND HIPPOCAMPAL NEUROGENESIS IN OFFSPRING IN RATS

Abstract Background Approximately 10 - 20 % pregnant women have been diagnosed with depression, and 3 - 6% pregnant women receive SSRI treatment. In Japan, it reported that approximately 1% of pregnant women (105 out of 10,000 births) were prescribed SSRIs during the perinatal period. Importantly, SSRIs crossed the placenta and may affect perinatal outcomes in infants exposed to these drugs during pregnancy in human. Several large cohort studies have been conducted, some finding significant differences in the risk of ASD and others not. In the present study, we created an animal model of a patient receiving medication during pregnancy and examined changes in the offspring`s behavior and brain structure. Aims & Objectives We created an animal model of a patient receiving medication during pregnancy and examined changes in the offspring`s behavior and brain structure in rats. Methods We used pregnant female Wistar rats. Paroxetine was administered daily from ED12.5 to ED21.5, covering the last 9–12 days of pregnancy. Oral sondes were used to keep rodents at a constant daily dose, and paroxetine 1 mg / kg / day or paroxetine 2.5 mg / kg / day or saline was given to the control group. The control group received saline daily. We evaluated spontaneous locomotor activity using the open field test (OF), spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze test (EPM) in male offspring at PD30. BrdU-positive cells in hippocampus were counted by fluorescence microscope. Results Locomotor activities significantly increase in paroxetine 2.5 mg group compare to a control group. The paroxetine 2.5 mg group spent less time in the closed arm compared to the control and paroxetine 1 mg groups in EPM. The number of BrdU-positive cells was significantly increased in the paroxetine 2.5 mg group compared to the control group. There was tendency to be a positive correlation between spontaneous activity and the number of BrdU-positive cells. Discussion & Conclusions In this study, it was revealed that oral administration of paroxetine during pregnancy induces hyperactivities and impulsivities in offspring, and increased neurogenesis in hippocampus of rats. There was a positive correlation between locomotor activity and the amount of neurogenesis. SSRI administration during pregnancy may affect the neurodevelopment of the newborn infant.