Stress-induced elevations of γ-aminobutyric acid type a receptor-active steroids in the rat brain

A 3α-hydroxy A-ring-reduced metabolite of progesterone, 3α-hydroxy-5α-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3α,21-dihydroxy-5α-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of γ-aminobutyric acid (GABA) receptors designated GABAA in the central nervous system. With specific radioimmunoassays, rapid (<5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swim stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (>3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function.