Ethanol-induced elevations in neuroactive steroids reach physiologically relevant concentrations that are capable of enhancing GABAergic transmission. A large body of evidence from multiple laboratories suggests that ethanol-induced elevations of GABAergic neuroactive steroids contribute to several behavioral effects of ethanol in rodents. Neuroactive steroids have been shown to modulate ethanol’s anticonvulsant effects (VanDoren et al. 2000), sedation (Khisti et al. 2003), impairment of spatial memory (Matthews et al. 2002; Morrow et al. 2001), anxiolytic-like (Hirani et al. 2005), antidepressant-like (Hirani et al. 2002), and pro-aggressive (Fish et al. 2001) actions. Most of these behavioral responses are prevented by pretreatment with finasteride and/or by prior adrenalectomy (Hirani et al. 2002; 2005; VanDoren et al. 2000). The sedative-hypnotic effect of ethanol is partially blocked by adrenalectomy (Khisti et al. 2003). Importantly, administration of 5α-dihydroprogesterone, the immediate precursor of 3α,5α-THP, to adrenalectomized rats restores effects of ethanol, showing that brain synthesis of neuroactive steroids can modulate effects of ethanol (Khisti et al. 2003). However, neuroactive steroids do not appear to influence the motor incoordinating effects of ethanol, since neither finasteride administration nor adrenalectomy diminish
