Acute application of ethanol (50 and 100 mM) to freshly isolated rat hippocampal slices increases tissue levels of 3α,5α-THP (Sanna et al. 2004). In addition, application of progesterone (the 3α,5α-THP precursor), CB34 (a peripheral benzodiazepine receptor agonist), or γ-hydroxybutyric acid, all of which promote steroidogenesis, also increases tissue levels of 3α,5α-THP. The increase in 3α,5α-THP induced by ethanol, progesterone, CB34, or γ-hydroxybutyric acid is prevented by pretreatment with the neuroactive steroid inhibitor finasteride. Furthermore, this increase in 3α,5α-THP levels is capable of potentiating GABAA receptor function, measured by recordings of spontaneous mIPSCs. Ethanol increases mIPSC amplitude and frequency in a time-and concentration-dependent manner: the effect is observed within the first 3 min, then it is reduced at 10 min and reappears after 30 min. In contrast, the decay time is increased 30 min after ethanol exposure. However, pretreatment with finasteride inhibits the increase in mIPSC amplitude and decay time constant at 30 min, but has no effect on mIPSC frequency, suggesting that the presynaptic action of ethanol is not mediated by an increase in neuroactive steroid content (Sanna et al. 2004).
