Prolonged exposure to alcohol: effect on CRF mRNA levels, and CRF- and stress-induced ACTH secretion in the rat.
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 +/- 12 mg%. At the end of the 7-day period, basal plasma ACTH levels were 69 +/- 10 pg/ml in control rats and 121 +/- 23 pg/ml in EtOH animals (P less than or equal to 0.01). Resting corticosterone levels were 39 +/- 11 ng/ml in control animals, and 101 +/- 24 ng/ml in EtOH rats (P less than or equal to 0.01). In all experiments described here, there was no statistical difference (P greater than 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 micrograms ovine CRF per rat caused dose-related increases in plasma ACTH levels measured 10 min later. All doses of CRF also significantly (P less than or equal to 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 microgram) with larger increases in plasma ACTH levels than control rats, the only statistical difference (P less than or equal to 0.01) between control and EtOH rats was observed following administration of 10 micrograms CRF, which caused a blunted response in EtOH animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Rivier
C
C
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
Imaki
T
T
Vale
W
W
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000494:pharmacology; D004597:Electroshock; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D015347:RNA Probes; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
D015347:RNA Probes; D012333:RNA, Messenger; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone