The scientific understanding of fear and anxiety – in both normal and pathological forms – is presently limited by a predominance of studies that employ male animals and Pavlovian fear conditioning-centered paradigms that restrict and assess specific behaviors (e.g., freezing) over brief sampling periods and overlook the broader contributions of the spatiotemporal context to an animal’s behavioral responses to threats. Here, we use a risky “closed economy” system – in which the need to acquire food and water and the need to avoid threats are simultaneously integrated into rats’ lives – to examine sex differences in mitigating threat risk while foraging. Rats lived for an extended period (∼2 months) in enlarged chambers that consisted of a safe, bedded nest and a risky foraging area where footshocks could be delivered unpredictably. We observed that male and female rats utilized different strategies for responding to the threat of footshock. Whereas male rats increased the size of meals consumed to reduce overall time spent foraging, female rats sacrificed their metabolic needs in order to avoid shocks. Ovarian hormone fluctuations were shown to exert slight but reliable rhythmic effects on risky decision-making in gonadally-intact female rats. However, this did not produce significant differences in approach-avoidance trade-offs between ovariectomized and intact female groups, suggesting that male-female sex differences are not due to the activational effects of gonadal hormones, but rather are likely to be organized during early development.
Significance Statement The National Institutes of Health (NIH) has recently mandated that all NIH-funded research must include balanced samples of each sex, but the initiative does little to address the reasons why researchers have avoided including female animals in their studies, which includes the perceived difficulty and high-cost of controlling for estrous cycle-related variability and their effects on behavior. Here, we utilize a longitudinal design to measure sex differences and the temporal variability of ovarian hormones on fear, anxiety, and risky-decision making continuously, and demonstrate functional differences in fear and anxiety behaviors between male and female rats that are independent of estrous cycle fluctuations.
Authors report no conflict of interest.