Elsevier

Brain Research

Volume 561, Issue 1, 4 October 1991, Pages 157-161
Brain Research

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

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Abstract

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 (3α-hydroxy-5α-pregnan-20-one; 1.25, 5.0, and 10 μm) and pregnanolone (3α-hydroxy-5β-pregnan-20-one; 2.5, 5.0, and 10 μg) elicited anxiolytic effects and, at the highest dose tested, allopregnanolone resulted in sedation. In contrast, the 3β-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 3α-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.

Keywords

Steroid
Allopregnanolone
Picrotoxin
Plus-maze
Anxiety
Sedation
Intracraial administration

Cited by (0)

This work was supported by NIMH Grant MH 31850 and a Research Scientist Development Award (NIMH MH 00651) to C.K.K.

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The authors thank Dr. R. H. Purdy for the generous gift of allopregnanolone and pregnanolone.