GABAergic Neurosteroids Mediate the Effects of Ethanol on Long-Term Potentiation in Rat Hippocampal Slices

The study investigated the effects of ethanol on long-term potentiation (LTP) in the CA1 region of rat hippocampal slices, focusing on the role of GABAergic neurosteroids. It was found that 60 mM ethanol completely blocked LTP, and this effect was enhanced at lower ethanol concentrations in the presence of the neurosteroid (3α5α)-3-hydroxypregnan-20-one, which potentiates GABA-A receptors. The blockade of LTP by ethanol was reversed by coadministration of a cyclodextrin that removes lipophilic neurosteroids, or by using finasteride, which inhibits the synthesis of 5α-reduced neurosteroids. These findings suggested that the acute production of GABA-A receptor-enhancing neurosteroids was crucial in mediating ethanol's effects on LTP.