Neuroactive Steroids Inhibit Spinal Reflex Potentiation by Selectively Enhancing Specific Spinal GABAA Receptor Subtypes

The study demonstrated that neuroactive steroids, specifically progesterone, inhibited spinal reflex potentiation by enhancing specific spinal GABAA receptor subtypes in ovariectomized rats. Progesterone increased the expression of GABAA receptor subunits α2, α3, α4, and δ, leading to reduced spinal reflex activity. This effect was mediated through neurosteroid metabolites, as it was blocked by finasteride, an inhibitor of neurosteroid synthesis, but not by the progesterone receptor antagonist RU486. Additionally, neurosteroids like allopregnanolone and 3α,5α-tetrahydrodeoxycorticosterone also attenuated spinal reflex potentiation, and the inhibition was reversed by the GABAA receptor antagonist bicuculline. The findings suggested that the modulation of spinal reflexes by progesterone was dependent on neurosteroid synthesis rather than direct progesterone receptor activation.