Systemic administration of moderate doses of ethanol (1–2.5 g/kg) increases brain and plasma levels of (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP), (3α,5α)-3,21-dihydroxypregnan-20-one (3α,5α-THDOC), and their precursors in rodents (Barbaccia et al. 1999; Gabriel et al. 2004; Khisti et al. 2005; Korneyev et al. 1993; Morrow et al. 1998; 1999; O’Dell et al. 2004; Serra et al. 2003; VanDoren et al. 2000). The ethanol-induced increase in neuroactive steroids is mediated by the hypothalamic–pituitary–adrenal (HPA) axis, since it is no longer observed immediately following adrenalectomy/gonadectomy in rats (Khisti et al. 2003; O’Dell et al. 2004; Porcu et al. 2004). However, ethanol can increase neuroactive steroids in hippocampal slices from both intact (Sanna et al. 2004) and adrenalectomized/gonadectomized rats (Follesa et al. 2006) and this finding is associated with an enhancement of GABAergic inhibition that can be blocked by the neuroactive steroid biosynthesis inhibitor finasteride (Sanna et al. 2004).
