Background: Prenatal ethanol exposure results in hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stress in the adult animal. In contrast, an early environmental manipulation, termed "postnatal handling," has been shown to result in decreased and/or less prolonged HPA activity in response to moderate stressors throughout the lifespan of the animal. The effects of both prenatal ethanol exposure and postnatal handling on HPA activity may be mediated by altered feedback regulation of the HPA axis. The present study tested the hypothesis that postnatal handling could attenuate the impact of prenatal ethanol exposure on hormonal responses to stressors.
Methods: Male and female Sprague Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups were either handled (H) or nonhandled (NH) during the preweaning period and were tested at 4 to 5 months of age. Animals were subjected to a 60 min restraint stress, 3 hr after intraperitoneal injection with either saline (SAL) or a synthetic glucocorticoid, dexamethasone-21-phosphate (DEX), in order to examine HPA responsiveness after DEX blockade of endogenous HPA activity. Blood samples were collected via jugular cannulae immediately before restraint (0 min), during restraint (10, 30, and 60 min), and 30 min after the termination of restraint (90 min).
Results: For both males and females, DEX administration significantly reduced plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations compared with SAL administration. H animals showed greater suppression of HPA activity (i.e., lower ACTH and/or CORT levels) than NH animals regardless of prenatal group. In addition, E females from both the H and NH treatments showed elevated ACTH and CORT after both SAL and DEX administration, whereas H and NH E males showed elevations in ACTH and CORT only after SAL, compared with their PF and C counterparts.
Conclusions: These data extend results from previous studies that demonstrated HPA hyperresponsiveness in E animals. The finding that E females but not males exhibit elevated ACTH and CORT after DEX administration suggests that prenatal ethanol exposure results in sex-specific alterations of HPA feedback. Consistent with previous data, handling in itself reduced the HPA response to restraint stress. However, handling did not attenuate either HPA hyperresponsiveness or feedback deficits in E animals.