Neurosteroids block the memory-impairing effects of ethanol in mice

Using a win-shift foraging paradigm to assess working memory in C57BL/6 mice, the memory-enhancing effect of low doses of the neurosteroids 5-pregnen-3 beta-ol-20-one [pregnenolone (PE)], 5-pregnen-3 beta-ol-20-one sulfate [pregnenolone sulfate (PS)], 5-androsten-3 beta-ol-17-one [dehydroepiandrosterone (DHEA)], and 5-androsten-3 beta-ol-17-one sulfate [dehydroepiandrosterone sulfate (DHEAS)] were demonstrated. The neurosteroids 5 beta-pregnan-3 alpha-ol-20-one [pregnanolone (PA)] and 5 beta-pregnan-3 beta-ol-20-one [epipregnanolone (EPI)] disrupted memory in this paradigm. PE, PS, DHEA, DHEAS, and PA were also capable of blocking the memory-impairing effect of 0.5 g/kg ethanol. EPI prevented PA from blocking the effect of ethanol. The influence of these compounds on memory and their interactions on this behavior are consistent with their actions on the GABAA system.