Glucocorticoid Fast Feedback Is Not Altered in Rats Prenatally Exposed to Ethanol

Abstract

Animals exposed in utero to ethanol exhibit hormonal hyperresponsiveness to stressors in adulthood. One possible mechanism for this hyperresponsiveness is a deficit in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. The present study tested the hypothesis that a deficit in the fast feedback time domain may play a role in the hormonal hyperresponsiveness in ethanol-exposed rats. Sprague-Dawley offspring from prenatal ethanol (E), pair-fed (PF), and ad lib-fed control (C) groups were tested in two experiments. Experiment 1 used a swim stress paradigm and tested animals at the trough of the corticosterone (CORT) circadian rhythm. Experiment 2 used ether stress and tested animals at the peak of the circadian rhythm. Animals were injected subcutaneously with CORT or saline and were immediately subjected to either a 5-min swim stress or a 1-min ether stress. Half the animals were terminated immediately after stress (5-min postinjection), and the rest were terminated 25 min later. Plasma levels of CORT and ACTH were assayed to determine whether E animals differed from control animals in showing a CORT-induced blunting of the ACTH response to the stressor, indicating alterations in fast feedback regulation. Injection of CORT significantly blunted the ACTH response to swim stress (experiment 1) in E, PF, and C females and males, compared with their saline-injected counterparts. There were no significant differences among groups. Similarly, CORT-injected males in E, PF, and C groups all exhibited a significantly blunted ACTH response to ether stress (experiment 2). CORT-injected C females also exhibited a significantly blunted ACTH response to ether stress, whereas E females showed an obvious CORT decrease that approached significance. However, PF females showed a clear deficit in fast feedback regulation. Together, these data suggest that: (1) CORT injection can serve as a fast feedback signal that can blunt the ACTH response to a stressor; and (2) prenatal ethanol exposure does not produce a deficit in hypothalamic-pituitary-adrenal feedback regulation in the fast feedback time domain.

Prenatal ethanol exposure in rats alters serotonergic-mediated behavioral and physiological function

“…A significant interaction between prenatal treatment and postnatal day for both females [F(6, 162)=3.27, P<0.005] and males [F(6, 162)=2.27, P<0.05] indicated that prenatal ethanol and pair-feeding resulted in lower average pup weights on postnatal day 21 (Table 1). This result is consistent with previous findings from our laboratory of decreased birth and pre-weaning body weights (Hofmann et al 1999). There were no significant body-weight differences on the day of testing for either experiment.…”

“…The finding that saline injection results in hyperthermia, and does so preferentially in E and PF animals, is not unexpected. Injection stress activates the HPA axis and induces expression of stress-responsive genes, as shown by our laboratory and others, and differential responsiveness to stress is known to occur in E animals (Hofmann et al 1999;Kim et al 1999;Wong et al 2000;Dent et al 2000). Effects of pair-feeding in itself were also observed.…”

Effects of Mineralocorticoid and Glucocorticoid Receptor Blockade on Hypothalamic–Pituitary–Adrenal Function in Female Rats Prenatally Exposed to Ethanol

“…Thus, pair feeding is in some ways a type of prenatal stressor. Interestingly, we have previously shown that PF offspring themselves may exhibit hyperresponsiveness to stressors (Hofmann et al, 1999;Osborn et al, 1996), and the present findings suggest that CORT feedback deficits may partially mediate this hyperresponsiveness. However, as E and PF animals often differ in HPA hyperresponsiveness, it is possible that a different mechanism may be mediating alterations in these 2 groups.…”

“…Previous studies in our laboratory suggest that E animals have deficits in the intermediate but not the fast CORT feedback time domain. For example, administration of CORT results in similar blunting of the ACTH response to swim or ether stress in E and C animals (Hofmann et al, 1999), suggesting an intact functional response in the fast feedback time domain (within seconds to minutes of stressor onset) (Keller-Wood and Dallman, 1984) in E animals. In contrast, within the intermediate feedback time domain (2-10 hours after stress) (Keller-Wood and Dallman, 1984), we (Osborn et al, 1996) have shown that at the circadian peak both E males and females demonstrate significantly greater CORT and/or ACTH responses than pair-fed (PF) and C to ether stress administered 3 to 6 hours following HPA suppression by the GR agonist dexamethasone (DEX).…”

Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise

“…Therefore, pair-feeding may be considered a type of prenatal stressor, and adverse effects of pair-feeding itself on offspring behavioral and physiological responsiveness may be observed. For example, we have previously shown that PF offspring may exhibit hyperresponsiveness to stressors (Hofmann et al, 1999), and this may represent at least partially an effect of stress in addition to any nutritional effects of mild food restriction. The mechanisms underlying the effects of pair-feeding on development remain to be determined.…”