Failure of Acute Ethanol Administration to Alter Cerebrocortical and Hippocampal Allopregnanolone Levels in C 57 BL /6 J and DBA /2 J Mice

Background Ethanol ( E t OH ) administration increases brain allopregnanolone levels in rats, and this increase contributes to sensitivity to E t OH 's behavioral effects. However, E t OH 's effects on allopregnanolone may differ across species. We investigated the effects of acute E t OH administration on allopregnanolone, progesterone, and corticosterone levels in cerebral cortex and hippocampus of C 57 BL /6 J and DBA /2 J mice, 2 inbred strains with different alcohol sensitivity. Methods Naïve male C 57 BL /6 J and DBA /2 J mice received E t OH (1, 2, 3, or 4 g/kg, intraperitoneally [i.p.]) or saline and were euthanized 1 hour later. For the time‐course study, mice received E t OH (2 g/kg, i.p.) and were euthanized 15, 30, 60, and 120 minutes later. Steroids were measured by radioimmunoassay. Results Acute E t OH administration did not alter cerebrocortical and hippocampal levels of allopregnanolone and progesterone in these strains at any of the doses and time points examined. Acute E t OH dose‐dependently increased cerebrocortical corticosterone levels by 319, 347, and 459% in C 57 BL /6 J mice at the doses of 2, 3, and 4 g/kg, and by 371, 507, 533, and 692% in DBA /2 J mice at the doses of 1, 2, 3, and 4 g/kg, respectively. Similar changes were observed in the hippocampus. E t OH 's effects on cerebrocortical corticosterone levels were also time dependent in both strains. Moreover, acute E t OH administration time‐dependently increased plasma levels of progesterone and corticosterone. Finally, morphine administration increased cerebrocortical allopregnanolone levels in C 57 BL /6 J (+77, +93, and +88% at 5, 10, and 30 mg/kg, respectively) and DBA /2 J mice (+81% at 5 mg/kg), suggesting that the impairment in brain neurosteroidogenesis may be specific to E t OH . Conclusions These results underline important species differences on E t OH ‐induced brain neurosteroidogenesis. Acute E t OH increases brain and plasma corticosterone levels but does not alter cerebrocortical and hippocampal concentrations of allopregnanolone and progesterone in naïve C 57 BL /6 J and DBA /2 J mice.