Estradiol decreases rat depressive behavior by estrogen receptor beta but not alpha

17β-Estradiol (E2) may influence some of the sex differences in stress-related neuropsychiatric disorders, such as anxiety and depression. E2 may also modulate the hypothalamic-pituitary-adrenal axis function as a cortisol response to stress in women. This study explored the role of E2 (10 and 50 μg/rat) and selective estrogen receptor modulators: diarylpropionitrile (DPN, 10 μg/rat) and propyl pyrazole triol (PPT, 10 μg/rat), in anxiety and depressive behaviors in ovariectomized rats using an animal model. The study also examined the relationship between rats' affective behavior and the plasma corticosterone (CORT) levels in response to chronic repeated restraint stress and series of behavior tests. Ovariectomized rats administered 10 μg E2 and 10 μg DPN showed more central entries in the open field, more open-arm duration in the elevated plus maze, and less immobility duration in the forced-swim test compared with rats administered vehicle or 10 μg PPT. 10 and 50 μg E2 significantly increased plasma CORT levels when compared with vehicle, 10 μg DPN, or 10 μg PPT. There was no correlation between the rats' depressive behavior and their plasma CORT levels. These results suggest that the antidepressant effects of E2 may involve ERβ, but are independent of an enhanced CORT response to stress.