, Volume 186, Issue 3, pp 302–311

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

Original Investigation

DOI: 10.1007/s00213-005-0100-x

Cite this article as:
Walf, A.A., Sumida, K. & Frye, C.A. Psychopharmacology (2006) 186: 302. doi:10.1007/s00213-005-0100-x



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.


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.


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.


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.


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


Progestin Allopregnanolone 5α-pregnan-3α-ol-20-one Neurosteroid Sex differences Mood 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Alicia A. Walf
    • 1
  • Kanako Sumida
    • 1
  • Cheryl A. Frye
    • 1
    • 2
    • 3
  1. 1.Department of PsychologyThe University at Albany-SUNYAlbanyUSA
  2. 2.Department of Biological SciencesThe University at Albany-SUNYAlbanyUSA
  3. 3.Center for Neuroscience ResearchThe University at Albany-SUNYAlbanyUSA

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