Systemic ethanol administration elevates deoxycorticosterone levels and chronic ethanol exposure attenuates this response

Systemic ethanol administration is known to elevate levels of the GABAergic neuroactive steroid 3 alpha,21-,dihydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THDOC). 3 alpha,5 alpha-THDOC is synthesized from deoxycorticosterone (DOC) by metabolism in adrenals and brain. The present study investigated DOC levels in plasma and brain following ethanol administration to naive and ethanol-exposed rats. Rats were administered ethanol (2 g/kg, i.p.) or saline and DOC levels were measured in plasma and brain regions,by radioimmunoassay. Chronic ethanol-exposed rats were administered an ethanol challenge (2 g/kg, i.p.) following 15 days of ethanol liquid diet consumption. Ethanol administration markedly increased DOC levels in plasma, cerebral cortex, hippocampus, hypothalamus, cerebellum, and olfactory tubercle of naive rats. Ethanol challenge produced an attenuated elevation of DOC in rat plasma and brain following chronic ethanol consumption for 2 weeks. These findings suggest that acute ethanol increases DOC levels in ethanol naive rats and chronic ethanol consumption induces tolerance to ethanol-induced increases in DOC levels. (c) 2005 Elsevier B.V. All rights reserved.