Dose-dependent effects of chronic estrogen treatment on anxiety-related behavior in female mice

Abstract

Though estrogens are well known to regulate anxiety or fear-related behavior, controversial effects of estrogen replacement to ovariectomized rodents were reported. This inconsistency may be due to differences in the treating condition of estrogens, such as duration of administration and/or their total amount. The present study was conducted to address these issues by examining the effect of chronic treatment of estradiol benzoate (EB) in ovariectomized ICR/Sea mice with several different doses of EB and intermittent observation of anxiety-related behavior in several tests ［open field (OF), elevated plus maze (EPM), light-dark transition (LDT)］. The behavioral parameters of the tests were subjected to factor analysis. As the results of comparing the factorial scores for two extracted factors, it was indicated that the mice implanted with relatively higher-dose EB capsule were more anxious than the animals treated with vehicle and/or lower-dose EB. While, the mice treated with the lower-dose EB did not show apparent change of anxiety. Together, the findings in the present study suggest that the chronic estrogen treatment may have anxiogenic effects in higher doses, while the effects were not clear in lower doses.