Carbon dioxide reactivity predicts fear expression after extinction and retrieval-extinction in rats

Cues present during a traumatic event may result in maladaptive fear responses. These responses can be attenuated through extinction learning, which is a core component of exposure therapy. Exposure/extinction is effective for some, but not all. We recently demonstrated that carbon dioxide (CO2) reactivity predicts fear extinction memory and orexin activation, and that orexin activation predicts fear extinction memory, suggesting that a CO2 challenge may enable identifying whether an individual is a good candidate for an extinction-based approach. Another method to attenuate conditioned responses, retrieval-extinction, modifies the original associative memory via distinct neural mechanisms. The purpose of the present study was to examine whether we could replicate previous findings that retrieval-extinction is more effective than extinction at preventing the return of fear and that CO2 reactivity predicts fear memory after extinction. We also examined whether CO2 reactivity predicts fear memory after retrieval-extinction.

创伤事件过程中出现的环境线索可引发适应不良的恐惧反应。此类反应可通过消退学习（extinction learning）得以减弱，而消退学习是暴露疗法（exposure therapy）的核心组成部分。暴露/消退疗法对部分人群有效，但并非适用于所有个体。我们此前的研究证实，二氧化碳（CO2）反应性可同时预测恐惧消退记忆与食欲素（orexin）激活水平，且食欲素激活亦可预测恐惧消退记忆，这提示二氧化碳激发试验（CO2 challenge）或可用于甄别个体是否适合基于消退学习的干预方案。另一种减弱条件反应的方法为提取-消退（retrieval-extinction）范式，其可通过独特的神经机制重塑原始联想记忆。本研究旨在验证两项此前的研究结论：其一，提取-消退范式在阻止恐惧复返方面优于单纯消退学习；其二，二氧化碳反应性可预测单纯消退学习后的恐惧记忆。本研究同时探究了二氧化碳反应性是否可预测提取-消退范式操作后的恐惧记忆。