Social dominance predicts hippocampal glucocorticoid receptor recruitment and resilience to prenatal adversity

Abstract

The developing fetus is highly sensitive to prenatal stress, which may alter Hypothalamic-Pituitary-Adrenal (HPA) axis programming and increase the risk of behavioral disorders. There is high variability among the human population, wherein many offspring of stressed pregnancies display resilience to adversity, while the remainder displays vulnerability. In order to identify biological substrates mediating between resilience or vulnerability to prenatal adversity, we exposed stress-resistant Dominant (Dom) and stress-sensitive Submissive (Sub) mice to mild prenatal restraint stress (PRS, 45 min on gestational days (GD) 15, 16 and 17). We hypothesized that PRS would differentially alter prenatal programming of limbic regions regulating the HPA axis and affect among Dom and Sub offspring. Indeed, PRS increased Sub offspring’s serum corticosterone, and exaggerated their anxiety- and depressive-like behavior, while Dom offspring remained resilient to the hormonal and behavioral consequences of PRS. Moreover, PRS exposure markedly facilitated glucocorticoid receptor (GR) recruitment to the hippocampus among Dom mice in response to restraint stress, which may be responsible for their resilience to stressful challenge. These findings suggest proclivity to adaptive or maladaptive prenatal programming of hippocampal GR recruitment to be inheritable and predictable by social dominance or submissiveness.