Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys.
BACKGROUND
The metabolites of deoxycorticosterone (DOC) and progesterone, allotetrahydrodeoxycorticosterone and allopregnanolone, are potent endogenous neuroactive steroids that are increased in rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) axis activation by acute stress or ethanol administration. However, little data are available for male nonhuman primates.


OBJECTIVE
To determine DOC concentrations in plasma samples from 11 monkeys following challenge of the HPA axis with naloxone, corticotropin-releasing factor (CRF), dexamethasone, adrenocorticotropic hormone (ACTH) following dexamethasone pretreatment and ethanol.


METHODS
DOC levels were measured in monkey plasma by radioimmunoassay.


RESULTS
DOC levels were increased after naloxone (125 microg/kg and 375 microg/kg, respectively) and CRF administration (1 microg/kg), and decreased following dexamethasone (130 microg/kg) administration. ACTH (10 ng/kg) challenge, 4-6 h after 0.5 mg/kg dexamethasone, and administration of ethanol (1.0 g/kg and 1.5 g/kg) had no effect on DOC concentrations. DOC levels were positively correlated with cortisol and ACTH levels after the naloxone (375 microg/kg), CRF, and ACTH challenges. Finally, the suppression of DOC levels measured after dexamethasone was negatively correlated with subsequent alcohol self-administration.


CONCLUSIONS
These results suggest that DOC levels in monkeys are regulated by the HPA axis and may contribute to physiological responses following activation.
Porcu
Patrizia
P
Department of Psychiatry, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7178, USA.
Grant
Kathleen A
KA
Green
Heather L
HL
Rogers
Laura S M
LS
Morrow
A Leslie
AL
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism
D009292:Narcotic Antagonists; D009270:Naloxone; D000431:Ethanol; D003900:Desoxycorticosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone