Sexually Dimorphic Risk Mitigation Strategies in Rats

Abstract

The scientific understanding of fear and anxiety—in both normal and pathological forms—is presently limited by a predominance of studies that use 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 the lives of rats, 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 used different strategies for responding to the threat of footshock. Whereas male rats increased the size of meals consumed to reduce the 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.

The Risky Closed Economy: A Holistic, Longitudinal Approach to Studying Fear and Anxiety in Rodents

“…This strategy, coupled with a strong avoidance of the risky Foraging Zone during the ''Shock'' phase, allowed animals to continue to gain weight and minimized the amount of daily footshock received. The results of this study and future studies expanding on this paradigm (Helmstetter and Fanselow, 1993;Kim et al, 2014;Pellman et al, 2015Pellman et al, , 2017) support the ethological theory that animals integrate the risk of predation in their daily foraging and activity decisions (Lima and Dill, 1990). Note that footshock is not intended to represent predatory encounter per se, but is used to broadly model the risk of predation while foraging.…”

“…Increased experimenter interaction (handling, feeding, and frequent transport). Pellman et al, 2015Pellman et al, , 2017; Figure 1C, top right). According to Predatory Imminence theory, which proposes that organisms' momentary perception of predation risk determines their defensive behavioral topography , the subtle changes in meal patterns and avoidance resulting from these shock parameters in the RCE resemble ''pre-encounter'' defensive reactions to threat Helmstetter and Fanselow, 1993).…”

Sex differences in fear regulation and reward seeking behaviors in a fear-safety-reward discrimination task

“…Taking into account the lack of conditioned inhibition of freezing in the females, the females may no longer be as motivated to seek rewards in the face of adverse footshocks. This would be consistent with the report that female rats sacrifice their metabolic needs in order to avoid shocks more than males (Pellman et al, 2017).…”

Sex differences in reward- and punishment-guided actions

“…Females demonstrate reduced preference for riskassociated rewards during a risky decision-making task (Orsini et al, 2016), as well as increased latency to perform a risky choice. Female rats also display reduced foraging for food and water in a randomly punished context, despite both sexes demonstrating a comparable reduction in time spent in this context (Pellman, Schuessler, Tellakat, & Kim, 2017). More importantly, this mirrors observations of reward motivated behavior in humans, and suggests that increased responsiveness to risk of punishment (rather than blunted reward sensitivity) may be responsible for increased vulnerability to anxiety symptoms in females (Sheynin et al, 2014).…”