Resistant and generalized fear are hallmark symptoms of Post-Traumatic Stress Disorder (PTSD). Given PTSD is highly comorbid with addiction disorders indicates a maladaptive interaction between fear and reward circuits. To investigate learning processes underlying fear, reward and safety, we trained male rats to discriminate among a fear cue paired with footshock, a reward cue paired with sucrose and an explicit safety cue co-occurring with the fear cue in which no footshocks were delivered. In an attempt to emulate aspects of PTSD, we pre-exposed male rats to a stressor (15 unsignaled footshocks) before training them to fear, reward and safety cues, and subsequent fear and reward extinction. Prior stress did not produce any significant impairments on conditioned inhibition to a safety cue compared to non-stressed controls. However, in subsequent fear extinction, prior stress profoundly impaired fear reduction to an extinguished fear cue. Prior stress also significantly reduced reward seeking to a reward-associated cue throughout training. Together, our data show that prior stress did not affect conditioned inhibition of fear to the same extent as impairing fear extinction. These results have interesting implications on how safety circuits are organized and impacted by stress, leading to possibly new avenues of research on mechanisms of stress disorders, such as PTSD.

中文翻译：

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先验压力对恐惧和恐惧消退的条件抑制的差异作用。

抵抗力和普遍恐惧感是创伤后应激障碍（PTSD）的标志性症状。鉴于PTSD与成瘾症高度并存，说明恐惧和奖赏回路之间存在不良适应性相互作用。为了研究恐惧，奖励和安全性的学习过程，我们训练了雄性大鼠以区分与脚震配对的恐惧提示，与蔗糖配对的奖励提示以及与没有传递脚踩电击的恐惧提示同时出现的显式安全提示。为了模拟PTSD的各个方面，我们在训练雄性大鼠恐惧，奖励和安全暗示以及随后的恐惧和奖励灭绝之前，将它们预先暴露于压力源（15只无信号的足底震击器）。与非压力对照组相比，先前的压力对安全提示的条件抑制没有产生任何明显的损害。然而，在随后的恐惧消灭中，先前的压力极大地削弱了将恐惧减少为已熄灭的恐惧提示的能力。在整个训练过程中，先前的压力也显着降低了寻求与奖励相关的提示的奖励。总之，我们的数据表明，先前的压力并未像在消除恐惧方面一样影响对恐惧的有条件抑制。这些结果对安全电路如何组织和受压力影响具有有趣的意义，从而可能为研究压力障碍机制（如PTSD）开辟新的途径。我们的数据表明，先前的压力并未像在消除恐惧方面一样影响到对恐惧的有条件的抑制。这些结果对安全电路如何组织和受压力影响具有有趣的意义，从而可能为研究压力障碍机制（如PTSD）开辟新的途径。我们的数据表明，先前的压力并未像在消除恐惧方面一样影响到对恐惧的有条件的抑制。这些结果对安全电路如何组织和受压力影响具有有趣的意义，从而可能为研究压力障碍机制（如PTSD）开辟新的途径。