CHRONIC NEUROSTEROID TREATMENT ATTENUATES SINGLE-CELL GABA(A) RESPONSE AND ITS POTENTIATION BY MODULATORS IN CORTICAL-NEURONS

In previous studies we have observed that chronic neurosteroid 5 alpha -pregnan-3 alpha-ol-20-one (5 alpha 3 alpha) treatment produced downre gulation of the GABA(A) receptors, heterologous uncoupling, and decrea sed heterologous efficacy at the GABA(A) receptor complex in cultured mammalian cortical neurons. In this study, using whole cell recording, we examined the consequence of chronic 5 alpha 3 alpha (1 mu M; 5 day s) treatment on GABA-induced currents in isolated cortical neurons. We observed that the GABA current was decreased by 78% after 5 days trea tment of cortical cells with 1 mu M 5 alpha 3 alpha. We also observed decreased pentobarbital, and 5 alpha 3 alpha potentiation of GABA curr ents after chronic 5 alpha 3 alpha treatment. These findings support t he notion that GABA response, and its potentiation by pentobarbital, a nd neurosteroid, 5 alpha 3 alpha, are attenuated after chronic 5 alpha 3 alpha treatment.