Different effects of subchronic doses of 17-beta estradiol in two ethologically based models of anxiety utilizing female rats

Estrogen may have differing effects on 'anxiety' responses under different conditions. The current study tested the effects of estrogen on anxiety-like behavior when administered for 6-7 days in ovariectomized (OVX) female rats. Two animal paradigms were utilized; the elevated plus maze (EPM), measuring changes in innate fear of exploration of open spaces; and the social interaction test (SIT), measuring the exploration of a novel, same gender partner. In the EPM, estradiol-treated OVX females both entered and spent more time in the open arms than control OVX females, indicating an anxiolytic-like action of estradiol. In contrast, estradiol treated OVX females interacted less with the partner animal in the SIT compared with controls suggesting anxiogenic-like effects. The possible anxiogenic effect of estradiol in the SIT is supported by two findings: (1) the effect is reversed by the anxiolytic drug alprazolam and (2) estrogen did not affect locomotion and therefore, the reduced social interaction is not due to reduced activity. Acute administration of progesterone (5 mg/kg), which has anxiolytic properties, did not reverse estradiol-induced social interaction deficits, suggesting that lack of progesterone did not account for estradiol's anxiogenic effects. These results, while seemingly contradictory when interpreted within a unified concept of anxiety, may well reflect the ethological roles of reproductive hormones and their effects on different types of exploratory anxiety.