Failure of acute ethanol administration to alter cerebrocortical and hippocampal allopregnanolone levels in C57BL/6J and DBA/2J mice

Background: Ethanol (EtOH) administration increases brain allopregnanolone levels in rats, and this increase contributes to sensitivity to EtOH's behavioral effects. However, EtOH's effects on allopregnanolone may differ across species. We investigated the effects of acute EtOH administration on allopregnanolone, progesterone, and corticosterone levels in cerebral cortex and hippocampus of C57BL/6J and DBA/2J mice, 2 inbred strains with different alcohol sensitivity. Methods: Naïve male C57BL/6J and DBA/2J mice received EtOH (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 EtOH (2 g/kg, i.p.) and were euthanized 15, 30, 60, and 120 minutes later. Steroids were measured by radioimmunoassay. Results: Acute EtOH 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 EtOH dose-dependently increased cerebrocortical corticosterone levels by 319, 347, and 459% in C57BL/6J mice at the doses of 2, 3, and 4 g/kg, and by 371, 507, 533, and 692% in DBA/2J mice at the doses of 1, 2, 3, and 4 g/kg, respectively. Similar changes were observed in the hippocampus. EtOH's effects on cerebrocortical corticosterone levels were also time dependent in both strains. Moreover, acute EtOH administration time-dependently increased plasma levels of progesterone and corticosterone. Finally, morphine administration increased cerebrocortical allopregnanolone levels in C57BL/6J (+77, +93, and +88% at 5, 10, and 30 mg/kg, respectively) and DBA/2J mice (+81% at 5 mg/kg), suggesting that the impairment in brain neurosteroidogenesis may be specific to EtOH. Conclusions: These results underline important species differences on EtOH-induced brain neurosteroidogenesis. Acute EtOH increases brain and plasma corticosterone levels but does not alter cerebrocortical and hippocampal concentrations of allopregnanolone and progesterone in naïve C57BL/6J and DBA/2J mice.