Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

Abstract Depression during pregnancy has been linked to in uterostress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10–20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stressmodel of maternal depression to test the hypothesis that in uteroantidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stressand antidepressant treatment on gene expression related to GABAergicand serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopramand mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in uterostress exposure, regardless of escitalopramtreatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdalaexpression of the chloride transporters KCC2 and NKCC1, which regulate GABAergicfunction. In contrast, prenatal escitalopramexposure alone elevated amygdalaexpression of 5-HT 1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdalaabated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stresscauses age-dependent deficits in anxiety-like behavior and amygdalafunction in female offspring, regardless of antidepressant exposure.