title: Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis.
abstract: Pregnenolone (PREG) is an endogenous neuroactive steroid that is increased in rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) activation by acute stress or ethanol administration. Plasma levels of PREG metabolites are altered by pharmacological challenges of the HPA axis, however little is known about HPA regulation of PREG levels in monkeys. PREG concentrations were determined by radioimmunoassay in plasma samples from cynomolgus monkeys, following challenge with naloxone (125 and 375 microg/kg), corticotropin-releasing factor (CRF; 1 microg/kg), dexamethasone (130 microg/kg), adrenocorticotropic hormone (ACTH; 10 ng/kg; 4-6 h after 0.5 mg/kg dexamethasone) and ethanol (1.0 and 1.5 g/kg). Naloxone increased PREG levels, while CRF appeared to increase metabolism of PREG to deoxycorticosterone (DOC). ACTH, administered after dexamethasone, reduced PREG levels, despite an increase in plasma cortisol. Ethanol did not alter PREG levels. Changes in PREG levels were correlated with changes in DOC levels after naloxone 125 microg/kg, CRF, ethanol 1.5 g/kg, and dexamethasone challenges. Furthermore, dexamethasone-induced changes in PREG levels were correlated with subsequent alcohol intake. These data suggest that PREG responses to dexamethasone challenge may represent a trait marker of alcohol drinking. The lack of effect of ethanol on PREG levels suggests differential regulation in non-human primates vs. rodents.
authors.affiliation: Department of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7178, USA.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Porcu
authors.forename: Laura S M
authors.initials: LS
authors.lastname: Rogers
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Morrow
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Grant
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011284:Pregnenolone / Q000097:blood*; D012646:Self Administration
chemical_list: D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D009270:Naloxone; D000431:Ethanol; D003900:Desoxycorticosterone; D011284:Pregnenolone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone