Adaptation of the hypothalamic-pituitary-adrenal axis to chronic ethanol stress.
The ability of chronic ethanol stress to alter hypothalamic-pituitary-adrenal (HPA) axis function in a manner similar to that previously reported for other chronic stress treatments was evaluated. Injection of male Sprague-Dawley or Long-Evans rats with ethanol (1-4 g/kg i.p., 20% v/v in saline) resulted in a rapid and large rise in serum corticosterone levels with maximal levels produced by a dose of 2 g/kg ethanol. Higher doses of ethanol did not increase the maximum corticosterone response above those produced by 2 g/kg ethanol but they extended the duration of the peak response. Chronic treatment with ethanol stress (1-3 weeks) produced signs of hyperstimulation of the HPA axis as indicated by adrenal hypertrophy and thymus involution. There was, however, adaptation of the HPA axis to the chronic ethanol treatment. The corticosterone response to ethanol on the last day of treatment was significantly less than on the first day of treatment, even though serum ethanol levels at the time of both measures were equivalent. There also were no signs of impaired negative feedback control of glucocorticoid secretion in the chronic-ethanol-treated rats. They exhibited a normal corticosterone response to 1 h of restraint and a normal shut-off of the stress response. There was also no down-regulation of type I or type II adrenal steroid receptors in the hippocampus of chronic ethanol-stress-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Spencer
R L
RL
Department of Neuroendocrinology, Rockefeller University, New York, NY.
McEwen
B S
BS
D000222:Adaptation, Physiological; D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004361:Drug Tolerance / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011987:Receptors, Steroid / Q000378:metabolism; D013312:Stress, Physiological / Q000139:chemically induced / Q000503:physiopathology*; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors
D011987:Receptors, Steroid; D000431:Ethanol; D003345:Corticosterone