Effects of prenatal ethanol exposure on regulation of basal hypothalamic–pituitary–adrenal activity and hippocampal 5-HT1A receptor mRNA levels in female rats across the estrous cycle

SummaryPrenatal ethanol exposure, like other early adverse experiences, is known to alter hypothalamic–pituitary–adrenal (HPA) activity in adulthood. The present study examined the modulatory effects of the gonadal hormones on basal HPA regulation and serotonin Type 1A receptor (5-HT1A) mRNA levels in adult female rats prenatally exposed to ethanol (E) compared to that in females from pair-fed (PF) and ad libitum-fed control (C) conditions.We demonstrate, for the first time, long-lasting consequences of prenatal ethanol exposure for basal corticosterone (CORT) regulation and basal levels of hippocampal mineralocorticoid (MR), glucocorticoid (GR) and serotonin Type 1A (5-HT1A) receptor mRNA, as a function of estrous cycle stage: (1) basal CORT levels were higher in E compared to C females in proestrus but lower in E and PF compared to C females in estrus; (2) there were no differences among groups in basal levels of adrenocorticotropin (ACTH), estradiol or progesterone; (3) hippocampal MR mRNA levels were decreased in E compared to PF and C females across the estrus cycle, with the greatest effects in proestrus, whereas E (but not PF or C) females had higher hippocampal GR mRNA levels in proestrus than in estrous and diestrus; (4) 5-HT1A mRNA levels were increased in E compared to PF and C females in diestrus. That alterations were revealed as a function of estrous cycle stage suggests a role for the ovarian steroids in mediating the adverse effects of ethanol. Furthermore, it appears that ethanol-induced nutritional effects may play a role in mediating at least some of the effects observed.The resetting of HPA activity by early environmental events could be one mechanism linking early life experiences with long-term health consequences. Thus, changes in basal CORT levels, a shift in the MR/GR balance and alterations in 5-HT1A receptor mRNA could have important clinical implications for understanding the secondary disabilities, such as an increased incidence of depression, in children with FASD.