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

Eliza M Greiner,Iris Müller,Makenzie R Norris,Ka H Ng,Susan Sangha

doi:10.1016/j.bbr.2019.111903

Abstract

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.

Highlights

Clinical disorders arising from maladaptive emotion regulation present a large burden on society worldwide
We show females exhibit a significantly different behavioral profile than males in a task that tests for reward, fear and safety cue discrimination, as well as conditioned inhibition and extinction
This data adds to the growing body of evidence of sex differences in fear regulation and highlights the advantages of using more complex learning paradigms with additional behavioral measurements

Summary

Introduction

Clinical disorders arising from maladaptive emotion regulation present a large burden on society worldwide. Many of these disorders show comorbidity, for example, addiction with anxiety disorders (Grant et al, 2016). Cues signifying safety have the power to modulate fear and reward-seeking behaviors by informing the organism whether or not the environment is safe (Walasek, Wesierska, & Zieliński, 1995). Safety, fear and reward behaviors, and the circuitries governing these behaviors, are intertwined. The majority of studies on reward and fear processing have been conducted in parallel, investigating the circuitries separately in primarily male subjects. If we hope to understand and treat comorbid disorders resulting from maladaptive emotion regulation, increased efforts in investigating how these circuitries integrate their functions to influence behavior is needed in both male and female subjects

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Conclusion