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

Reward availability and the potential for danger or safety potently regulate 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 did not suppress conditioned freezing in the presence of a safety cue, nor did they extinguish their freezing response, whereas males did 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 suggest females were able to regulate this behavior in response to the safety cue, suggesting they were able to discriminate between fear and safety cues but did not demonstrate this with conditioned suppression of freezing behavior. However, levels of darting in this study were too low to make any definitive conclusions. In summary, females showed a significantly different behavioral profile than males in a task that tested 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.