Department of Psychological Sciences, USA.
Department of Psychological Sciences, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, USA.
Behav Brain Res. 2020 Mar 2;381:112414. doi: 10.1016/j.bbr.2019.112414. Epub 2019 Dec 28.
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.
抵抗和普遍恐惧是创伤后应激障碍（PTSD）的标志性症状。鉴于 PTSD 与成瘾障碍高度共病，这表明恐惧和奖励回路之间存在适应不良的相互作用。为了研究恐惧、奖励和安全的学习过程，我们训练雄性大鼠辨别与足底电击配对的恐惧线索、与蔗糖配对的奖励线索以及与恐惧线索同时出现但不给予足底电击的明确安全线索。为了尝试模拟 PTSD 的某些方面，我们在训练大鼠对恐惧、奖励和安全线索产生恐惧之前，先让它们暴露于应激源（15 次未标记的足底电击），然后进行随后的恐惧和奖励消退。与未受应激的对照组相比，先前的应激并没有对安全线索的条件抑制产生任何显著的损害。然而，在随后的恐惧消退中，先前的应激会严重损害对已消退的恐惧线索的恐惧减少。先前的应激也显著减少了对与奖励相关线索的奖励寻求，贯穿整个训练过程。总的来说，我们的数据表明，先前的应激对恐惧消退的影响程度不如对恐惧消退的抑制作用大。这些结果对于安全回路的组织方式以及应激对其的影响具有有趣的意义，为应激障碍（如 PTSD）的机制研究开辟了新的途径。
