Maternal separation alters glucocorticoid signaling in the nucleus accumbens of female mice

Early life stress (ELS) has been identified as a significant contributing factor in numerous neuropsychiatric disorders. In fact exposure to multiple traumatic early life events (4 + ) increases the risk of developing alcohol use disorders 7 fold and post-traumatic stress disorders 2 fold. Women are particularly vulnerable; they are twice as likely to develop a disorder following ELS than men. Maternal separation is commonly used to model ELS in rodents. We adapted the maternal separation model to develop a method for identifying mice with abnormal basal plasma corticosterone levels. We then applied this protocol to examine the effects of maternal separation on glucocorticoid signalling in the nucleus accumbens (NAc) and amygdala. We found that maternal separation increased basal plasma corticosterone levels in female but not male mice. We then categorized female mice that had been exposed to ELS as having either high, normal and low basal plasma corticosterone levels and compared them to control mice. Plasma corticosterone levels were significantly elevated in high ELS and reduced in low ELS mice compared to control and normal ELS mic respectively. There was no difference between plasma corticosterone levels in normal ELS and control mice. We then measured glucocorticoid receptor (GR) and corticosterone levels in the NAc and amygdala. ELS mice with high basal plasma corticosterone also had elevated NAc corticosterone levels. No differences were identified in the NAc between low ELS, normal ELS or control groups. There was a trend for reduced NAc GR expression in both high and low ELS mice compared to normal ELS and control groups. The data suggest that maternal separation alters glucocorticoid signaling in the NAc in females and not males, which supports findings in human studies. Future studies will explore the effects of stress on glucocorticoid signalling following ELS.