The anxiolytic effect of allopregnanolone is associated with gonadal hormonal status in female rats

Eur J Pharmacol. 2001 Apr 6;417(1-2):111-6. doi: 10.1016/s0014-2999(01)00865-2.

Abstract

The behavioural display in the plus-maze, an established experimental model of anxiety, was studied in rats injected into the lateral brain ventricle (i.c.v.) with the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone). Female rats under different gonadal hormonal status were chosen. Allopregnanolone enhanced exploration of the open arms in both estrous rats and ovariectomized estrogen and progesterone primed rats. No effect was observed in diestrous 1 and ovariectomized not-primed rats. In all cases, the plus-maze locomotor-exploratory behaviour was not affected by allopregnanolone. The GABA(A) receptor antagonist, bicuculline (9.8 microM i.c.v.) reversed the allopregnanolone action in the ovariectomized primed rats. When bicuculline was injected i.c.v. in conjunction with allopregnanolone, the anxiogenic effect of bicuculline was reversed by the highest dose (25 microM) of allopregnanolone only. These results suggest that allopregnanolone exerts an anxiolytic action interacting with the GABA(A) receptor in an estrogen-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Bicuculline / pharmacology
  • Dose-Response Relationship, Drug
  • Estrogens / pharmacology
  • Estrus / physiology
  • Exploratory Behavior / drug effects
  • Female
  • GABA Antagonists / pharmacology
  • Hormones / metabolism*
  • Maze Learning / drug effects
  • Motor Activity / drug effects
  • Ovariectomy
  • Ovary / metabolism*
  • Pregnanolone / pharmacology*
  • Progesterone / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Anxiety Agents
  • Estrogens
  • GABA Antagonists
  • Hormones
  • Progesterone
  • Pregnanolone
  • Bicuculline