Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain.
Robert H. Purdy; A. Leslie Morrow; Perry H. Moore; Steven M. Paul
Proceedings of the National Academy of Sciences1991
Summary (paraphrased)
This foundational study demonstrated that acute stress sharply elevates GABA-A receptor-active steroids — including THDOC and allopregnanolone — in the rat brain. Using swim stress with biochemical quantification, the authors showed that the brain's inhibitory neurosteroid tone is dynamically coupled to stress exposure. The work established the core observation the entire stress-neurosteroid-GABA literature rests on: stress co-releases GABAergic neurosteroids alongside glucocorticoids. It remains among the most-cited empirical anchors for all later THDOC physiology.
Why it’s in the systems review
This is the empirical root of the stress–THDOC story Powers leans on: without stress-induced neurosteroid surges, there is no substrate for an "excess held in place by feedback loops" model. It serves as the founding observation that later work (Reddy 2003; Cadeddu 2025) builds on, and it defines the normal physiology that any pathological-excess hypothesis must be measured against.
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