Impaired fear extinction, combined with the likelihood of fear relapse after exposure therapy, contributes to the persistence of many trauma-related disorders such as anxiety and post-traumatic stress disorder. Identifying mechanisms to aid fear extinction and reduce relapse could provide novel strategies for augmentation of exposure therapy. Exercise can enhance learning and memory and augment fear extinction of traumatic memories in humans and rodents. One factor that could contribute to enhanced fear extinction following exercise is the mammalian target of rapamycin (mTOR). mTOR is a translation regulator involved in synaptic plasticity and is sensitive to many exercise signals such as monoamines, growth factors, and cellular metabolism. Further, mTOR signaling is increased after chronic exercise in brain regions involved in learning and emotional behavior. Therefore, mTOR is a compelling potential facilitator of the memory-enhancing and overall beneficial effects of exercise on mental health. The goal of the current study is to test the hypothesis that mTOR signaling is necessary for the enhancement of fear extinction produced by acute, voluntary exercise. We observed that intracerebral-ventricular administration of the mTOR inhibitor rapamycin reduced immunoreactivity of phosphorylated S6, a downstream target of mTOR, in brain regions involved in fear extinction and eliminated the enhancement of fear extinction memory produced by acute exercise, without reducing voluntary exercise behavior or altering fear extinction in sedentary rats. These results suggest that mTOR signaling contributes to exercise-augmentation of fear extinction.

恐惧消退受损，加上暴露治疗后恐惧复发的可能性，导致许多与创伤相关的疾病持续存在，如焦虑和创伤后应激障碍。确定有助于消除恐惧和减少复发的机制可以为加强暴露疗法提供新的策略。运动可以增强人类和啮齿动物的学习和记忆，并增强对创伤记忆的恐惧消退。可能有助于增强运动后恐惧消退的一个因素是雷帕霉素 (mTOR) 的哺乳动物靶标。mTOR 是一种参与突触可塑性的翻译调节剂，对许多运动信号（如单胺、生长因子和细胞代谢）敏感。更远，在涉及学习和情绪行为的大脑区域进行长期运动后，mTOR 信号传导增加。因此，mTOR 是运动对心理健康的记忆增强和整体有益影响的一个引人注目的潜在促进剂。目前研究的目的是检验 mTOR 信号对于增强由急性自愿运动产生的恐惧消退是必要的假设。我们观察到 mTOR 抑制剂雷帕霉素的脑室内给药降低了与恐惧消退有关的大脑区域中磷酸化 S6（mTOR 的下游靶标）的免疫反应性，并消除了由急性运动产生的恐惧消退记忆的增强，而不会减少自主运动行为或改变久坐大鼠的恐惧消退。