Brain regional differences in social encounter-induced Fos expression in male and female rats after post-weaning social isolation

Early life adversity has been related to a number of psychological disorders including mood and other disorders that can manifest as inappropriate or aggressive responses to social challenges. The present study used post-weaning social isolation (PSI) in rats, a model of early life adversity, to examine its effects on Fos protein expression produced by exposure to a novel social encounter. We have previously reported that the social encounter-induced increase in Fos expression in the medial prefrontal cortex observed in group-housed controls (GRP) was attenuated in rats that had experienced PSI. Here we assessed Fos expression in other brain regions thought to be involved in emotion regulation and social behavior. Male and female rats were housed in same-sex groups or in isolation (ISO) for 4 weeks beginning on postnatal day (P) 21 and were exposed to a single 15 min social encounter with a novel same-sex conspecific on P49. Fos positive cells were assessed using immunohistochemistry in 16 regions within the forebrain. Exposure to a novel conspecific increased Fos expression in the forebrain of GRP rats in a region- and sex-specific fashion. This increase was blunted or absent in ISO rats within many regions including cortical regions, thalamus, habenula, dentate gyrus, lateral septum, and basolateral amygdala. In several regions, the increase in Fos was greater in male than in female group housed rats. Negative relationships were observed between social interactions and Fos in some regions. Forebrain hypofunction produced by early-life adversity may be involved in socially inappropriate behavior.