Hypothalamic-pituitary-adrenal axis feedback regulation in rats prenatally exposed to ethanol

• Main Author: Hofmann, Candace Erica
• Language: English
• Published: 2009
• Online Access: http://hdl.handle.net/2429/8128

Animals exposed to ethanol 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 hypothalamicpituitary- adrenal (HPA) 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. Expt 1 utilized a swim stress paradigm and tested animals at the trough of the corticosterone (CORT) circadian rhythm; Expt 2 utilized ether stress and tested animals at the peak of the circadian rhythm. Animals were injected sc 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 post injection) and the rest were terminated 25 min later. Plasma levels of CORT and adrenocorticotropin (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 (Expt 1) in E, PF and C females and males compared to 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 (Expt 2) . CORT injected C females also exhibited a significantly blunted ACTH response to ether stress, while E females showed a clear decrease in plasma CORT that approached significance, indicating functional fast feedback in E and C females. 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, 2) prenatal ethanol exposure does not produce a deficit in HPA feedback regulation in the fast feedback time domain.