Stress-Induced Deoxycorticosterone-Derived Neurosteroids Modulate GABA A Receptor Function and Seizure Susceptibility

The study provided evidence that stress-induced neurosteroids derived from deoxycorticosterone (DOC) modulated GABA(A) receptor function and affected seizure susceptibility. During stress, DOC was metabolized into neurosteroids like THDOC, which had anticonvulsant properties. In rats, acute stress increased THDOC levels and raised seizure thresholds. Similarly, small doses of DOC increased THDOC and seizure thresholds, effects reversed by finasteride, a 5alpha-reductase inhibitor. DOC also protected mice against various seizures, with its effects reversed by finasteride and partially by indomethacin. DHDOC, another metabolite, also potentiated GABA-activated currents, suggesting its role in DOC's antiseizure activity. Thus, DOC mediated stress effects on seizures through conversion to neurosteroids affecting GABA(A) receptors.