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Inhibiting 5α-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats

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Abstract

Rationale

Greater incidence of anxiety and depressive disorders of women compared to men may be due in part to progesterone (P) and its neuroactive metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), acting in limbic regions, such as the amygdala.

Objective

If P's metabolism via 5α-reduction to 3α,5α-THP in the amygdala is critical for antianxiety and antidepressive behavior, then blocking 5α-reductase in the amygdala of female rats is likely to attenuate the antianxiety and antidepressive effects of high progestin levels from both endogenous and exogenous sources.

Methods

Naturally receptive female rats with high endogenous estrogen (E2) and P and ovariectomized (ovx) rats administered E2 (10 μg) and P (500 μg) subcutaneously were administered finasteride (10 μg/μl), a Type II 5α-reductase inhibitor, or vehicle to the amygdala. Anxiety behavior (open field, elevated plus maze, defensive freezing) and depressive behavior (Porsolt forced swim test) were assessed.

Results

There were similar effects of finasteride administration to the amygdala to attenuate antianxiety behavior in naturally receptive and ovx, hormone-primed rats. Finasteride administration significantly decreased central entries in the open field, decreased open arm time in the elevated plus maze, increased defensive freezing in response to footshock, and increased time spent immobile compared to vehicle.

Conclusions

Thus, formation and subsequent actions of 3α,5α-THP in the amygdala may be important for antianxiety and antidepressive effects.

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Acknowledgements

This research was supported by grants from the National Science Foundation (IBN98-96263; IBN03-16083), National Institute of Mental Health (MH0676980), Whitehall Foundation (096-010), and Ronald McNair Research Program to support minority undergraduates. Technical assistance provided by Lesley Ann Cole, Kate Fagan-Solis, and Dr. Madeline Rhodes is greatly appreciated. All experiments comply with the current laws of the United States of America, where they were performed.

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Authors and Affiliations

  1. Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA

    Alicia A. Walf, Kanako Sumida & Cheryl A. Frye

  2. Department of Biological Sciences, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA

    Cheryl A. Frye

  3. Center for Neuroscience Research, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA

    Cheryl A. Frye

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  1. Alicia A. Walf
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  2. Kanako Sumida
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Correspondence to Cheryl A. Frye.

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Walf, A.A., Sumida, K. & Frye, C.A. Inhibiting 5α-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats. Psychopharmacology 186, 302–311 (2006). https://doi.org/10.1007/s00213-005-0100-x

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