Hypothalamic-pituitary-adrenal axis and ethanol modulation of deoxycorticosterone levels in cynomolgus monkeys

Rationale: 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 ug/kg and 375 ug/kg, respectively) and CRF administration (1 ug/kg), and decreased following dexamethasone (130 ug/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 ug/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. © Springer-Verlag 2005.