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

Walf AA, Sumida K, Frye CA

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

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, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), acting in limbic regions, such as the amygdala. OBJECTIVE: If P's metabolism via 5alpha-reduction to 3alpha,5alpha-THP in the amygdala is critical for antianxiety and antidepressive behavior, then blocking 5alpha-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 (E(2)) and P and ovariectomized (ovx) rats administered E(2) (10 mug) and P (500 mug) subcutaneously were administered finasteride (10 mug/mul), a Type II 5alpha-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 3alpha,5alpha-THP in the amygdala may be important for antianxiety and antidepressive effects.

Published 25 May 2006 in Psychopharmacology (Berl), 186(3): 302-11.
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