Glucocorticoid receptor expression in the stress-limbic circuitry is differentially affected by prenatal alcohol exposure and adolescent stress.

The dense expression of glucocorticoid receptors (GR) within the amygdala, medial prefrontal cortex (mPFC) and paraventricular nucleus of hypothalamus (PVN) mediates many aspects of emotional and stress regulation. Importantly, both prenatal alcohol exposure (PAE) and adolescent stress are known to induce emotional and stress dysregulation. Little is known, however, about how PAE and/or adolescent stress may alter the expression of GR in the amygdala, mPFC, and PVN. To fill this gap, we exposed PAE and control adolescent male and female rats to chronic mild stress (CMS) and assessed GR mRNA expression in the amygdala, mPFC, and PVN immediately following stress or in adulthood. We found that the effects of PAE on GR expression were more prevalent in the amygdala, while effects of adolescent stress on GR expression were more prevalent in the mPFC. Moreover, PAE effects in the amygdala were more pronounced during adolescence and adolescent stress effects in the mPFC were more pronounced in adulthood. GR expression in the PVN was affected by both PAE and adolescent stress. Finally, PAE and/or adolescent stress effects were distinct between males and females. Together, these results suggest that PAE and adolescent CMS induce dynamic alterations in GR expression in the amygdala, mPFC, and PVN, which manifest differently depending on the brain area, age, and sex of the animal. Additionally, these data indicate that PAE-induced hyperresponsiveness to stress and increased vulnerability to mental health problems may be mediated by different neural mechanisms depending on the sex and age of the animal.