NEUROSTEROID MODULATION OF NATIVE AND RECOMBINANT GABA(A) RECEPTORS

1. The pioneering work of Hans Selye over 50 years ago demonstrated th at certain steroid metabolites can produce a rapid depression of centr al nervous system activity. 2. Research during the last 10 years has e stablished that such effects are mediated by a nongenomic and specific interaction of these steroids with the brain's major inhibitory recep tor, the GABA(A) receptor. 3. Here we describe the molecular mechanism of action of such steroids and review attempts to define the steroid binding site on the receptor protein. The therapeutic potential of suc h neurosteroids is discussed.