Abstract
Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT+/+) and heterozygous (SERT+/-) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT+/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT+/+ female offspring and total social behavior in fluoxetine exposed adult SERT+/- male offspring. Furthermore, SERT+/- males appeared less social during adulthood compared to SERT+/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood.
Highlights
During pregnancy, about 7–13% of women are depressed or suffer from depressive symptoms (Bennett et al, 2004)
Post hoc analysis revealed that dams from the maternal early life stress (MS)-VEH group had a significantly shorter gestation period compared to all other groups
The present study was the first to assess the effects of MS and perinatal FLX exposure, both separately and combined, on both juvenile and adult social behavior in male and female offspring
Summary
About 7–13% of women are depressed or suffer from depressive symptoms (Bennett et al, 2004). SSRIs are able to cross the placenta and can be found in breast milk, reaching the developing child (Heikkinen et al, 2003; Noorlander et al, 2008). There is an ongoing debate about whether the benefits of treating the mother’s depression during pregnancy and the postpartum period outweigh the potential health risks for the child. Both maternal mood and SSRI treatment have been increasingly linked to changes in social development in children. The long-term impact of the complex interaction between maternal depression and perinatal SSRI treatment on social behavior in the offspring is not fully understood yet
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