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.

Summary Rodents in the wild are under nearly constant threat of aerial predation and thus have evolved adaptive innate defensive behaviors, such as freezing or fleeing, in response to a perceived looming threat. Here we employed an ethologically relevant paradigm to study innate fear of aerial predators in male and female rats during a goal-oriented task. Rats foraging for food in a large arena encountered either a 2D or 3D looming stimulus, to which they instinctively fled back to a safe nest. When facing a direct aerial threat, female rats exhibited a greater fear response than males and this divergence maintained when exposed to the environment on subsequent days with no predator interaction, suggesting stronger contextual fear in female rats. These results may have relevance toward exploring neurobiological mechanisms associated with higher diagnosis rates of fear and anxiety-related disorders in women as compared with men.

Pavlovian fear conditioning, which offers the advantage of simplicity in both the control of conditional and unconditional stimuli (CS, US) presentation and the analysis of specific conditional and unconditional responses (CR, UR) in a controlled laboratory setting, has been the standard model in basic and translational fear research. Despite 100 years of experiments, the utility of fear conditioning has not been trans-situationally validated in real-life contexts. We thus investigated whether fear conditioning readily occurs and guides the animal’s future behavior in an ecologically-relevant environment. To do so, Long-Evans rats foraging for food in an open arena were presented with a tone CS paired with electric shock US to their dorsal neck/body that instinctively elicited escape UR to the safe nest. On subsequent test days, the tone-shock paired animals failed to exhibit fear CR to the CS. In contrast, animals that encountered a realistic agent of danger (a looming artificial owl) paired with a shock, simulating a plausible predatory strike, instantly fled to the nest when presented with a tone for the first time. These results highlight the possibility of a nonassociative, rather than standard associative, fear process providing survival function in life-threatening situations that animals are likely to encounter in nature.

Basic research of fear and anxiety in rodents has historically utilized a limited set of behavioral paradigms, for example, Pavlovian (classical) fear conditioning, the elevated plus-maze, or inhibitory (passive) avoidance. These traditional paradigms measure a limited selection of variables over a short duration, providing only a "snapshot" of fear and anxiety-related behavior. Overreliance on these paradigms and such behavioral snapshots ultimately lead to a narrow understanding of these complex motivational states. Here, we elaborate on the closed economy; a seldom-used paradigm that has been modified to comprehensively study fear and anxiety-related behavior and neurocircuitry in rodents. In this modified "Risky Closed Economy (RCE)" paradigm, animals live nearly uninterrupted in behavioral chambers where the need to acquire food and water and avoid threat is integrated into the task. Briefly, animals are free to acquire all of their food and water in a designated foraging zone. An unsignaled, unpredictable threat (footshock) is introduced into the foraging zone after a baseline activity and consumption period to model the risk of predation, which is then removed for a final extinction assessment. This longitudinal design, wherein data from a multitude of variables are collected automatically and continuously for 23 h/day over several weeks to months, affords a more holistic understanding of the effects of fear and anxiety on day-today behavior. Also, we discuss its general benefits relevant to other topics in neuroscience research, its limitations, and present data demonstrating for the first time The Risky Closed Economy's viability in mice.

Pavlovian fear conditioning, which offers the advantage of simplicity in both the control of conditioned and unconditioned stimuli (CS, US) presentation and the analysis of specific conditioned and unconditioned responses (CR, UR) in a controlled laboratory setting, has been the standard model in basic and translational fear research. Despite 100 years of experiments, the utility of fear conditioning has not been trans-situationally validated in real-life contexts. We thus investigated whether fear conditioning readily occurs and guides the animal's future behavior in an ecologically-relevant environment. To do so, Long-Evans rats foraging for food in an open arena were presented with a tone CS paired with electric shock US to their dorsal neck/body that instinctively elicited escape UR to the safe nest. On subsequent test days, the tone-shock paired animals failed to exhibit fear CR to the CS. In contrast, animals that encountered a realistic agent of danger (a looming artificial owl) paired with a shock, simulating a realistic predatory strike, instantly fled to the nest when presented with a tone for the first time. These results illustrate the survival function and precedence of a nonassociative process, rather than associative conditioning, in life-threatening situations that animals are likely to encounter in nature.

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An author name was incorrectly spelled as Kisho M. Kukuoka. The correct spelling is Kisho M. Fukuoka.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.