Effect of repeated exposure to alcohol on the response of the hypothalamic-pituitary-adrenal axis of the rat: II. Role of the length and regimen of alcohol treatment.
BACKGROUND
Prior exposure to alcohol alters the adrenocorticotropin hormone (ACTH) response to a second drug challenge administered several days later. We used three models of alcohol treatment to investigate the mechanisms that may be involved in this phenomenon.


METHODS
Adult male rats were exposed to alcohol vapors daily for 3 days (4-4.5 hr/day) and then were exposed to shocks or an intragastric injection of alcohol 7 days later (group A); were injected daily with alcohol (4.5 g/kg intragastrically) for 3 days and then exposed to shocks or an intragastric injection of alcohol 7 days later (group B); or were exposed to alcohol vapors for 6 days and exposed to shocks or an intragastric injection 24 hr later (group C). Control animals were not exposed to the vapors or received the appropriate vehicle.


RESULTS
Compared with animals administered the vehicle, rats of groups A and B that had been exposed to alcohol all exhibited a significantly decreased ACTH response to a second drug challenge. In contrast, their ACTH response to footshocks was statistically comparable to that of vehicle-pretreated animals. Rats of group C that had been exposed to alcohol for 6 days also showed decreased ACTH release when injected with alcohol 7 days later while responding normally to shocks. Measurement of anterior pituitary pro-opiomelanocortin indicated that alcohol pretreatment had produced a 54% increase of these transcripts in group C and a 27% decrease in group A. There were no changes in pituitary receptors type 1 for corticotropin-releasing factor (CRFR1) in any of the groups.


CONCLUSIONS
Regardless of whether they are delivered shortly before an acute alcohol injection or several days earlier, alcohol vapors or injections interfere with the ACTH response to the drug but not to shocks. Our results also suggest that changes in ACTH responses may not be correlated directly with small changes in pituitary pro-opiomelanocortin or CRFR1 mRNA levels.
Rivier
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Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA. crivier@salk.edu
Lee
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D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone