Prolonged exposure to alcohol: effect on CRF mRNA levels, and CRF- and stress-induced ACTH secretion in the rat

Abstract

We have conducted studies in intact adult male rats, designed to examine the effect of a 3- or 7-day exposure to alcohol (EtOH) on the pituitary's response to corticotropin-releasing hormone (CRF) or stress, and on CRF expression in the hypothalamus. In a first series of experiments, rats exposed to EtOH vapors for 7 days had mean blood alcohol levels (BAL) of 127 ± 12mg%. At the end of the 7-day period, basal plasma ACTH levels were 69 ± 10pg/ml in control rats and 121 ± 23pg/ml in EtOH animals ( P ⩽ 0.01). Resting corticosterone levels were 39 ± 11ng/ml in control animals, and 101 ± 24ng/ml in EtOH rats ( P ⩽ 0.01). In all experiments described here, there was no statistical difference ( P > 0.05) between the body weights of controls (animals kept in chambers with normal atmosphere) and EtOH-exposed animals. In control animals, the injection of 0.3–10 μg ovine CRF per rat caused dose-related increases in plasma ACTH levels measured 10 min later. All doses of CRF also significantly ( P ⩽ 0.01) stimulated ACTH secretion by EtOH rats, but there was no clear dose-response curve. Though EtOH-treated animals responded to the lower dose of CRF (0.3 μg) with larger increases in plasma ACTH levels than control rats, the only statistical difference ( P ⩽ 0.01) between control and EtOH rats was observed following administration of 10 μg CRF, which caused a blunted response in EtOH animals. These results suggested that alcohol caused an increased sensitivity and decreased maximum responsiveness of the pituitary to CRF. In a second series of experiments, we examined the effect of a 7-day exposure to EtOH on the hypothalamic-pituitary-adrenal response to mild electroshocks (1.0 mA, 0.5 s duration, 2 shocks/min, 10 min total duration). At the end of the 7-day period, BAL were 158 ± 20mg%, and basal ACTH values were 58 ± 9pg/ml for control rats and 175 ± 52pg/ml for EtOH animals ( P ⩽ 0.01). Resting corticosterone levels for control and EtOH rats were 32 ± 10and115 ± 26ng/ml, respectively ( P ⩽ 0.01). Though stress-induced ACTH levels were statistically equivalent ( P > 0.05) in control and EtOH rats (978 ± 220vs768 ± 153pg ACTH/ml), the increase over basal values were significantly ( P ⩽ 0.01) smaller in rats exposed to alcohol. A third series of experiments investigated the effect of a 3- or 7-day exposure to EtOH on CRF expression in the hypothalamus. Both periods of EtOH exposure caused an approximate 2-fold increase ( P ⩽ 0.01) in CRF mRNA levels in the hypothalamus. These results indicate that exposure of male rats to alcohol vapors for 7 days significantly alters the activity of the hypothalamic-pituitary-adrenal axis.