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

Abstract

Reward availability and the potential for danger or safety potently regulates emotion. Despite women being more likely than men to develop emotion dysregulation disorders, there are comparatively few studies investigating fear, safety and reward regulation in females. Here, we show that female Long Evans rats do not suppress conditioned freezing in the presence of a safety cue, nor do they extinguish their freezing response, whereas males do both. Females were also more reward responsive during the reward cue until the first footshock exposure, at which point there were no sex differences in reward seeking to the reward cue. Darting analyses indicate females might be able to regulate this behavior in response to the safety cue, suggesting they might be able to discriminate between fear and safety cues but do not demonstrate this with conditioned suppression of the freezing behavior. However, levels of darting in this study were too low to make any clear conclusions. In summary, females showed a significantly different behavioral profile than males in a task that tests the ability to discriminate among fear, safety and reward cues. This paradigm offers a great opportunity to test for mechanisms that are generating these behavioral sex differences in learned safety and reward seeking.

Ventrolateral periaqueductal gray neurons prioritize threat probability over fear output

“…If not freezing, conditioned suppression, or nose poke cessation then perhaps another measure of fear? Danger cues elicit active fear responses: escape-like behaviors such as darting (Greiner et al, 2018; Gruene et al, 2015). However, darting is prevalent in females, but less so in males.…”

Sex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex

“…Despite there being evidence that sex differences may contribute to how animals engage with and process rewarding stimuli, sex is an often overlooked component when determining how an animal's internal state modulates reward-related behaviors. In fact, recent studies have shown that male and female mice exhibit divergent learning and decision-making strategies in reward-guided behaviors 20,41,42 . Moreover, sex differences in mPFC reward representations were shown to underlie some of the behavioral differences observed in nonsocial reward-seeking 43 .…”