Anxiolytic effects of 3 alpha-hydroxy-5 alpha[beta]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor

Brain Res. 1991 Oct 4;561(1):157-61. doi: 10.1016/0006-8993(91)90761-j.


The effects of intracerebroventricular administration of reduced metabolites of progesterone on locomotor activity and on exploration in the elevated plus-maze were assessed in adult female rats. Allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one; 1.25, 5.0, and 10 micrograms) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one; 2.5, 5.0, and 10 micrograms) elicited anxiolytic effects and, at the highest dose tested, allopregnanolone resulted in sedation. In contrast, the 3 beta-hydroxy-epimer of allopregnanolone was without effect in either behavioral paradigm. The anxiolytic response to pregnanolone was blocked by picrotoxin (0.75 mg/kg, i.p.), a dose that by itself did not affect behavior in the plus-maze. These data suggest that the anxiolytic effect of 3 alpha-hydroxy metabolites of progesterone is mediated by brain GABAA receptors in a stereospecific manner, and are in good agreement with the well-documented in vitro effects of these steroids as potent modulators of the GABAA receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Female
  • Injections, Intraventricular
  • Pregnanolone / pharmacology*
  • Progesterone / metabolism*
  • Rats
  • Receptors, GABA-A / drug effects*


  • Anti-Anxiety Agents
  • Receptors, GABA-A
  • Progesterone
  • Pregnanolone