Adrenal steroid hormones and ethanol self-administration in male rhesus macaques.
BACKGROUND
Hypothalamic-pituitary-adrenal (HPA) axis hormones have neuroactive metabolites with receptor activity similar to ethanol.


OBJECTIVE
The present study related HPA hormones in naïve monkeys to ethanol self-administration.


METHODS
Morning plasma adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone (DOC), aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were measured longitudinally in male rhesus macaques (Macaca mulatta) induced to drink ethanol followed by access to ethanol (4 % w/v, in water) and water 22 h/day for 12 months.


RESULTS
During ethanol access, DOC increased among non-heavy (average intake over 12 months ≤3.0 g/kg/day, n = 23) but not among heavy drinkers (>3.0 g/kg/day, n = 9); aldosterone was greater among heavy drinkers after 6 months. The ratio of DOC/aldosterone decreased only among heavy drinkers after 6 or12 months of ethanol self-administration. ACTH only correlated significantly with DHEA-S, the ratio of cortisol/DHEA-S and DOC after the onset of ethanol access, the former two just in heavy drinkers. Baseline hormones did not predict subsequent ethanol intake over 12 months, but baseline DOC correlated with average blood-ethanol concentrations (BECs), among all monkeys and heavy drinkers as a group. During ethanol access, aldosterone and DOC correlated and tended to correlate, respectively, with 12-month average ethanol intake.


CONCLUSIONS
Ethanol self-administration lowered ACTH and selectively altered its adrenocortical regulation. Mineralocorticoids may compensate for adrenocortical adaptation among heavy drinkers and balance fluid homeostasis. As DOC was uniquely predictive of future BEC and not water intake, to the exclusion of aldosterone, GABAergic neuroactive metabolites of DOC may be risk factors for binge drinking to intoxication.
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, 97006, USA, helmsc@ohsu.edu.
Christa M
CM
Helms
Byung
B
Park
Kathleen A
KA
Grant
D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology*; D000435:Alcoholic Intoxication / Q000378:metabolism / Q000523:psychology; D000437:Alcoholism / Q000378:metabolism / Q000523:psychology; D000818:Animals; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D014882:Water-Electrolyte Balance
D000305:Adrenal Cortex Hormones; D008901:Mineralocorticoids