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

Abstract

Summary Prenatal 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) 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.

Prenatal Alcohol Exposure Alters Response of Kisspeptin‐ir Neurons to Estradiol and Progesterone in Adult Female Rats

“…These findings extend our previous showing differential effects of high concentrations of E 2 on PAE compared to control females. Under most conditions, basal corticosterone levels do not differ among prenatal groups, but during proestrus, when E 2 levels are high, PAE females have increased basal corticosterone levels compared to controls (Lan et al, 2009b; Sliwowska et al, 2008). …”

Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

“…Moreover, there is a bidirectional regulatory relationship between 5-HT and the HPA axis (44). We have shown that PAE animals exhibit increased hypothermic and anxiolytic responses and blunted ACTH responses to 8-OH-DPAT, a 5-HT 1a receptor agonist, compared with PF and C animals (26), and that E females show alterations in 5-HT 1A receptor levels in the hippocampus that are estrous cycle stage-dependent (62). Furthermore, it has been reported that the short allele of the SLC6A4 promoter variant, 5HTTLPR, increases the probability of neonatal irritability and stress responsiveness in rhesus monkeys exposed prenatally to alcohol and that this gene-environment interaction may affect psychosocial development (58).…”

Prenatal ethanol exposure enhances NMDAR‐dependent long‐term potentiation in the adolescent female dentate gyrus

“…In contrast to adults (Warren et al, 1995;Good et al, 1999), estradiol reduces LTP in the adolescent hippocampus (Ito et al, 1999). Pubertal estradiol is closely related to vaginal opening (Ojeda et al, 1976;Germain et al, 1978) and since vaginal opening is delayed in females following PNEE McGivern and Yellon, 1992;Sliwowska et al, 2008), pubertal estradiol levels might be reduced in females following PNEE. We were unable to determine estradiol levels in the current study and thus cannot confirm this hypothesis.…”