Inhibiting 5alpha-reductase in the amygdala attenuates antianxiety and antidepressive behavior of naturally receptive and hormone-primed ovariectomized rats.
BACKGROUND
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 (E2) and P and ovariectomized (ovx) rats administered E2 (10 microg) and P (500 microg) subcutaneously were administered finasteride (10 microg/microl), 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.
Walf
Alicia A
AA
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.
Sumida
Kanako
K
Frye
Cheryl A
CA
D058891:5-alpha Reductase Inhibitors; D000679:Amygdala / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D018120:Finasteride / Q000494:pharmacology*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D011374:Progesterone; D004958:Estradiol; D018120:Finasteride