Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF).

The acute i.p. administration of alcohol (EtOH) to freely moving, nonanesthetized rats caused dose-related elevations in plasma adrenocorticotropin (ACTH) and corticosterone levels. In vivo, injection of anticorticotropin-releasing factor (CRF) serum (i.v.) totally abolished this stimulatory effect, suggesting that the induction of CRF secretion by EtOH represents an essential modulator of its ability to release ACTH. Exposure to high levels of alcohol vapors for 7 days was accompanied by a decrease in hypothalamic CRF content. The acute exposure of cultured pituitary cells to 0.2% EtOH did not modify basal or CRF-induced ACTH release, whereas pretreatment of the cells with EtOH for 24 hr resulted in a marked decrease in both spontaneous and stimulated ACTH secretion. It is therefore possible that the long-term exposure to alcohol may result in an increase of CRF release by the median eminence, as well as in some loss of pituitary responsiveness. From these data, we hypothesize that the acute EtOH-induced activation of the hypothalamic-pituitary-adrenal axis probably takes place at the level of CRF-secreting neurons and that this effect may play a role in the disturbance of ACTH and corticosteroid secretion observed during chronic exposure to alcohol.