Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.

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Siblings share similar genetics and environments, however, their behavior can be quite different. To determine if within-litter variance in neonatal-maternal interactions predict adult sibling behavioral variance, we observed mother-pup interactions during postnatal days 1-8 in four Sprague-Dawley rat litters and measured adult offspring behavioral responses to social and physical novelty. Our results indicate that pup and maternal behavior varied by at least twofold within each litter, and that specific pup behaviors within each litter (perioral contact) were associated with increased maternal licking. Furthermore, siblings that received more licks and made more perioral contact during postnatal days 1-8 had longer latencies to approach novel objects in adulthood than siblings that received less licking and made less perioral contact. This within-litter variance in postnatal mother and pup behavior and offspring adult behavior indicates that early social dynamics within families are an important area to examine to understand the development of sibling variance.

In female mammals, the postpartum period involves dramatic shifts in many socioemotional behaviors. This includes a suppression of anxiety-related behaviors that requires recent physical contact with offspring. Factors contributing to differences among females in their susceptibility to the anxiety-modulating effect of offspring contact are unknown, but could include their innate anxiety and brain monoaminergic activity. Anxiety behavior was assessed in a large group of nulliparous female rats and the least-anxious and most-anxious tertiles were mated. Anxiety was assessed again postpartum after females were permitted or prevented from contacting their offspring 4 h before testing. Levels of dopamine β-hydroxylase (DBH, norepinephrine synthesizing enzyme) and tryptophan hydroxylase- 2 (TPH2, serotonin synthesizing enzyme) were measured in the brainstem and dorsal raphe, respectively. It was found that anxiety-related behavior in the two groups did not differ when dams were permitted contact with offspring before testing. Removal of the offspring before testing, however, differentially affected anxiety based on dams’ innate anxiety. Specifically, dams reverted back to their pre-mating levels of anxiety such that offspring removal slightly increased anxiety in the most-anxious females but greatly lowered anxiety in the least-anxious females. This reduction in anxiety in the least-anxious females after litter removal was associated with lower brainstem DBH. There was no relationship between females’ anxiety and dorsal raphe TPH2. Thus, a primary effect of recent contact with offspring on anxiety-related behavior in postpartum rats is to shift females away from their innate anxiety to a more moderate level of responding. This effect is particularly true for females with the lowest anxiety, may be mediated by central noradrenergic systems, and has implications for their ability to attend to their offspring.

The need to obtain data from individual laboratory animals has forced many researchers to singlyhouse rodents and small animals. Isolation is an abnormal condition for many species, and adverse effects of single-housing on physiology and behavior threaten the validity of experimental results and generalization to humans, who are also social. This study assessed the practical use of a housing device -dubbed "Buddy Barrier" (BB) -that allows rats social stimulation in a paired-housing situation while at the same time permitting the collection of individual measures that traditionally require individual-housing. To assess stress responses to the BB, adult male rats were single or pairhousing for several days with and without a BB in the cage and fecal corticosterone metabolites (fCORT), food intake and body weight were monitored. Plasma corticosterone and adrenal catecholamine levels were also assessed at the end of the housing manipulation. Stress hormone measures did not differ in paired vs. singly-housed rats and paired rats quickly habituated to the BB taken in and out of the cage. Barring a trend for paired rats to eat more in the first 4hrs of the dark, there was no difference in 24hr intakes or body weight gain between singly and paired-housed rats. While the BB attenuated 24hr intakes in both groups, intakes normalized to non-BB conditions by the third BB reintroduction. A device such as the BB can enhance the welfare of animals by providing social enrichment without compromising the integrity of experimental manipulations in protocols that traditionally have required single-housing.