Rapid anxiolytic activity of progesterone and pregnanolone in male rats

Rapid anxiolytic activity of progesterone and pregnanolone in male rats The effect of different doses of progesterone (1.0, 3.0, 10.0, 30.0, and 100.0 mg/kg) and pregnanolone (1.0, 3.0, 10.0, and 30.0 mg/kg) upon burying defensive and elevated plus-maze (EPM) tests was investigated in adult male rats and compared with the effects of diazepam (0.25. 0.50, 1.0, and 2.0 mg/kg). All drugs were suspended in a 0.2% methylcellulose solution and administered intraperitoneally 30 min prior to testing. Progesterone and pregnanolone were found to produce anxiolytic-like effects similar to those of diazepam. Thus, at certain doses, both drugs significantly increased the latency for burying and decreased the cumulative burying behavior, without modifying the number of shocks, and increased the time spent in the open arms of the maze, without affecting the spontaneous locomotor activity. These data clearly demonstrate that the defensive burying paradigm is useful to detect the anxiolytic-like properties of pregnanolone. An important finding was that progesterone produces significant behavioral effects 30 min after its administration. This finding suggests a rapid bioconversion of progesterone to its active ring-A reduced metabolites; however, the possibility remains that rapid behavioral effects of progesterone are due to a direct interaction with specific steroid receptors located on the plasma membrane, independently from the γ-aminobutyric acid A (GABA A ) receptor complex modulation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pharmacology Biochemistry and Behavior Elsevier

Rapid anxiolytic activity of progesterone and pregnanolone in male rats

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science Inc.
ISSN
0091-3057
eISSN
1873-5177
DOI
10.1016/S0091-3057(02)00722-0
Publisher site
See Article on Publisher Site

Abstract

The effect of different doses of progesterone (1.0, 3.0, 10.0, 30.0, and 100.0 mg/kg) and pregnanolone (1.0, 3.0, 10.0, and 30.0 mg/kg) upon burying defensive and elevated plus-maze (EPM) tests was investigated in adult male rats and compared with the effects of diazepam (0.25. 0.50, 1.0, and 2.0 mg/kg). All drugs were suspended in a 0.2% methylcellulose solution and administered intraperitoneally 30 min prior to testing. Progesterone and pregnanolone were found to produce anxiolytic-like effects similar to those of diazepam. Thus, at certain doses, both drugs significantly increased the latency for burying and decreased the cumulative burying behavior, without modifying the number of shocks, and increased the time spent in the open arms of the maze, without affecting the spontaneous locomotor activity. These data clearly demonstrate that the defensive burying paradigm is useful to detect the anxiolytic-like properties of pregnanolone. An important finding was that progesterone produces significant behavioral effects 30 min after its administration. This finding suggests a rapid bioconversion of progesterone to its active ring-A reduced metabolites; however, the possibility remains that rapid behavioral effects of progesterone are due to a direct interaction with specific steroid receptors located on the plasma membrane, independently from the γ-aminobutyric acid A (GABA A ) receptor complex modulation.

Journal

Pharmacology Biochemistry and BehaviorElsevier

Published: Jun 1, 2002

References

  • Anxiolytic effect of progesterone is mediated by the neurosteroid allopregnanolone at brain GABA A receptors
    Bitran, D; Shiekh, M; McLeod, M
  • The anxiolytic-like effects of the neurosteroid allopregnanolone: interactions with GABA A receptors
    Brot, MD; Akwa, Y; Purdy, RH; Koob, GF; Britton, KT
  • Anti-anxiety effects of progesterone and some of its reduced metabolites: an evaluation using the burying behavior test
    Picazo, O; Fernández-Guasti, A
  • Behaviorally selective effects of neuroactive steroids on plus-maze anxiety in mice
    Rodgers, RJ; Johnson, NJT
  • Anticholinergic properties of progesterone in the isolated ileum of the guinea-pig
    Rodriguez, R; Fernandez, G; Ramirez, R; Medina, M
  • Effect of flumazenil and diazepam on transient actions in defensive burying elicited by the social interaction experience in rats
    Saldivar-Gonzalez, JA; Gomez, C; Martinez-Lomeli, I; Arias, C

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