Effects of Pubertal Stress on Later Pup-Directed Behavior in Pregnant and Non-Pregnant Adult Female Mice

Abstract

Beginning in adolescence and throughout adulthood, women are at an increased risk for anxiety and mood disorders compared to men. Several risk factors for these disorders have been identified, but it is not clear how they interact. One such factor is pregnancy. The normative changes to the brain and behavior that occur during and after pregnancy are associated with an increased risk for anxiety and mood disorders. Exposure to adverse childhood experiences (ACEs) has also been associated with an increased risk of mood disorders, and compared to men, women appear to be particularly vulnerable to the lasting effects of stress that occurs during puberty. There is evidence that these factors interact and increase vulnerability to anxiety or mood disorders, but this relationship is not well understood. Previously, we found that adult female mice that had undergone chronic variable stress (CVS) in adolescence showed a blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress in late pregnancy. In postpartum humans, this same blunted maternal stress response has been correlated with an increased incidence of depressive symptoms. However, the consequences of this HPA blunting on behavior are not well understood. Of particular interest are maternal behaviors, such as pup retrieval in mice, which emerge during pregnancy due to vast changes in hormones and neural circuitry. The current study aims to examine the effects of CVS during adolescence on pup retrieval behaviors in pregnant and not-pregnant adult female mice. We hypothesized that exposure to chronic stress during puberty would disrupt the formation of maternal behavior in adult mice. Here, we found that pubertal stress disrupted the HPA axis response of CVS mice to behavioral testing. In addition, pubertal stress led to changes in behavior on a pup retrieval task