Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA_A receptor function and seizure susceptibility
Doodipala S Reddy, Michael A Rogawski
The Journal of Neuroscience2002
Summary (paraphrased)
Demonstrated that acute swim stress raises plasma THDOC (allotetrahydrodeoxycorticosterone) in rats and increases the seizure threshold, and that the 5alpha-reductase inhibitor finasteride reverses this stress-induced anticonvulsant effect by blocking conversion of deoxycorticosterone to DHDOC/THDOC. In hippocampal neurons, DHDOC and THDOC potentiated and directly activated GABA_A receptor chloride currents, establishing stress-derived neurosteroids as endogenous GABA_A modulators whose synthesis depends on 5alpha-reductase.
Why it’s in the corpus
Classic paper showing finasteride blocks stress-induced neurosteroid synthesis via 5alpha-reductase inhibition — direct mechanistic support for the hypothesis that 5alpha-reductase blockade disrupts endogenous GABAergic neurosteroid tone, a proposed mechanism in both PFS and PSSD.
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