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, revealing that ethanol inhibited LTP through mechanisms involving γ-aminobutyric acid-A receptors (GABA A Rs). It was found that 60 mM ethanol was required to completely block LTP, and this effect was enhanced by the presence of the neurosteroid (3α5α)-3-hydroxypregnan-20-one, which potentiates GABA A Rs. The study demonstrated that the block of LTP by ethanol could be reversed by agents that either bind and remove neurosteroids or inhibit their synthesis and effects on GABA A Rs. These findings suggested that GABA A R-enhancing neurosteroids played a crucial role in mediating ethanol's effects on LTP.