The role of ovarian hormones in risk aversion in female rats

Decision making involving risk of punishment is a cognitive process characterized by sex-specific phenotypes, with females exhibiting greater risk aversion than males. Although prior research has demonstrated that ovarian hormones, and estradiol (E2) in particular, contribute to increased risk aversion in females, the receptor mechanisms underlying these effects remain unknown. Further, it is unclear what role the other key ovarian hormone progesterone (P4) plays in female risk aversion. Accordingly, the current set of experiments were designed to address these gaps in knowledge of the hormonal basis of female risk-taking behavior. Female rats were trained in a punishment-based risky decision-making task, ovariectomized, and then retested in the decision-making task. Rats were then treated with estradiol benzoate (Experiment 1; EB), estrogen receptor (ER) agonists (Experiment 2) or progesterone (Experiment 3; P4) after daily test sessions for 7 days. Consistent with prior work, OVX increased risk taking, and EB administration attenuated this effect. Administration of an ERα agonist, either alone or with an ERβ agonist, similarly mitigated the effects of OVX on risk taking. In contrast, the ERβ agonist alone was ineffective in restoring risk aversion in OVX females. Control tests confirmed that the effects of the ERα agonist on risk taking were not due to altered food motivation or footshock sensitivity. Finally, P4 administration did not alter risk taking in OVX females and did not inhibit EB's behavioral effects. Collectively, these data reveal that E2 is the critical ovarian hormone that promotes female risk aversion; further, they suggest that the likely mechanism by which E2 influences risk aversion in females is through activation of ERα.