Prenatal exposure to selective serotonin reuptake inhibitors (SSRI) increases aggression and modulates maternal behavior in offspring mice

Abstract

Selective serotonin reuptake inhibitors (SSRI) are commonly prescribed antidepressant drugs in pregnant women. SSRIs cross the placental barrier and affect serotonergic neurotransmission in the fetus. Although no gross SSRI-related teratogenic effects were reported, infants born following prenatal exposure to SSRIs are at higher risk for various developmental abnormalities. The aim of this study was to examine the effects of prenatal SSRI on social and maternal behavior in mice. To this end, pregnant female dams were exposed to saline or fluoxetine (FLX) throughout pregnancy, and the behavior of the offspring was examined. The results indicate that in utero FLX increased aggression in adult males and delayed emergence of maternal behavior in adult females. Social exploration and recognition memory were not affected by prenatal FLX exposure. These findings support the notion that alterations in the development of serotonergic pathways following prenatal exposure to SSRIs are associated with changes in social and maternal behavior throughout life.

Maternal SSRI treatment during offspring development results in long-term behavioral, cellular, and neuroimaging disruptions

“…Complementing our findings on distinct effects of maternal FLX on dominance, recent work showed prenatal maternal FLX treatment decreased aggressive behaviors, while treatment extending postnatally increased aggressive behaviors in adult C57BL/6 male offspring (Kiryanova, Meunier, Vecchiarelli, Hill, & Dyck, 2016). However, another report showed increased aggression in male offspring of ICR dams exposed to only prenatal FLX (Svirsky, Levy, & Avitsur, 2016). The discrepancies in aggression findings between these two studies may reflect strain x drug interactions.…”

Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

“…Given the growing literature on the effects of serotonin on maternal care, it is perhaps not surprising that perinatal SSRIs alter maternal behavior in female offspring. However, to date only one study has been done in this area and findings from this work show that prenatal fluoxetine can reduce maternal behaviors of female offspring when they are mothers by reducing nest quality and delaying pup retrieval (Svirsky et al, 2016). Interestingly, these same prenatally R e v i s e d m a n u s c r i p t 16 SSRI-exposed female offspring showed more adaptability in maternal behaviors, with greater improvements in maternal care on postnatal day 2 and 3 than controls (Svirsky et al, 2016).…”

Antidepressant use during pregnancy and the risk of attention‐deficit/hyperactivity disorder in the children: a meta‐analysis of cohort studies

“…In theory, antidepressant drugs can pass the placental barrier and directly affect brain development by altering neurotransmission . Several preclinical studies have shown that gestational exposure to antidepressants affects the development of neurotransmitter systems, resulting in long‐lasting effects on the behaviour of offspring . However, animal studies are not always generalisable to the clinical situation.…”