Naloxone and ethanol modulation of plasma deoxycorticosterone and pregnenolone levels in cynomolgus monkeys

Deoxycorticosterone (DOC) and pregnenolone (PREG) are precursors of the potent endogenous neuroactive steroids allotetrahydrodeoxycorticosterone and allopregnanolone that are increased in rodent brain and plasma after acute stress or ethanol administration. However, no data are available for nonhuman primates. Steroid concentrations were measured by radioimmunoassay in plasma samples from eleven monkeys following naloxone or ethanol administration. Naloxone (125 and 375 ug/kg, i.m.) increased DOC levels 86 and 97%, respectively (p<0.01). PREG levels were also increased by naloxone challenge (222 and 216%, respectively? p<0.001). In contrast, ethanol administration (1.0 and 1.5 g/kg, i.g.) did not modify plasma DOC, PREG or cortisol levels in monkeys. DOC levels were positively correlated with cortisol or ACTH levels after the naloxone 375 ug/kg challenge, but not after ethanol challenge. PREG levels were not correlated with cortisol or ACTH levels after naloxone challenge. Dexamethasone (130 ug/kg, i.m.) decreased DOC levels by 42% (p<0.001), while ACTH (10 ng/kg, i.v.) challenge, 46 hours after 0.5 mg/kg dexamethasone, had no effect. DOC levels in monkeys appear to be modulated by the HPA axis, however, other factors influence DOC synthesis since exogenous ACTH had no effect on DOC levels after dexamethasone suppression. Ethanol had no effect on DOC or PREG levels in monkey plasma, suggesting that these steroids are differentially regulated in monkeys vs. rats. Supported by AA10564, UO1 AA13515 and AA13510.