Delayed unpaired extinction as a treatment for hyperarousal of the rabbit nictitating membrane response and its implications for treating PTSD.
Delayed unpaired extinction as a treatment for hyperarousal of the rabbit nictitating membrane response and its implications for treating PTSD.
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延迟不成对消退作为兔子瞬膜反应过度唤醒的治疗方法及其对治疗创伤后应激障碍（PTSD）的影响。
DOI：
10.1016/j.jpsychires.2018.01.007
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发表时间：
2018
影响因子：
4.8
通讯作者：
Burhans,LaurenB
中科院分区：
文献类型：
--
作者：
Schreurs,BernardG;Smith-Bell,CarrieA;Burhans,LaurenB
创伤后应激障碍（PTSD）的治疗很少在创伤后立即提供，通常在事件发生后延迟数周或数月。在一个兔眨眼条件反射模型的创伤后应激障碍，我们以前已经表明，介绍了一个音调条件刺激（CS）和休克非条件刺激（US）在一个明确的不成对的方式称为不成对的灭绝是有效的减少CS反应和US过度觉醒，即使休克强度降低8倍，elevated只有最小的反应。在这里，我们确定延迟交付的不成对灭绝是否仍然有效地消除过度觉醒。在CS-US配对之前和CS-US配对后一天、一周或一个月的未配对消退后，测试家兔对电击的敏感性。过度觉醒在条件反射后一天和一周就消失了，但一个月后还没有消失，这表明“治疗”的显著延迟会使过度觉醒持续存在。接下来，我们通过比较给予CS-US配对的兔子与给予明确的非配对CS和US呈现的兔子，在一天和一个月后测量过度觉醒，然后进行非配对消退和过度觉醒评估，来评估这种过度觉醒的持续性是否具有关联性。四周后，所有兔子的反应都有所增加，但只有接受CS-US配对的兔子显示出联合介导的过度觉醒显著增加。重要的是，配对和未配对组在未配对消退后均显示出反应水平增加，这表明治疗延迟太久可能不再有效，并可能导致全身性过度觉醒。
Treatment for PTSD (Post-traumatic stress disorder) is rarely available immediately after trauma and often delayed for weeks or months after an event. In a rabbit eyeblink conditioning model of PTSD, we have previously shown that presentations of a tone conditioned stimulus (CS) and shock unconditioned stimulus (US) in an explicitly unpaired manner known as unpaired extinction is effective in reducing CS responding and US hyperarousal even if shock intensity is reduced eight-fold and elicits only minimal responding. Here we determined if delayed delivery of unpaired extinction would still be effective in extinguishing hyperarousal. Rabbits were tested for sensitivity to shock before CS-US pairings and after six days of unpaired extinction presented a day, a week or a month after CS-US pairings. Hyperarousal was extinguished a day and a week after conditioning but not after a month suggesting a significant delay in “treatment” can make hyperarousal persist. We next assessed if this persistence of hyperarousal was associative by comparing rabbits given CS-US pairings to those given explicitly unpaired CS and US presentations, measuring hyperarousal a day and a month later, followed by unpaired extinction and hyperarousal assessment. After four weeks, there was an increase in responding for all rabbits but only rabbits receiving CS-US pairings showed a significant increase in associatively-mediated hyperarousal. Importantly, both paired and unpaired groups showed increased levels of responding after unpaired extinction suggesting treatment delayed for too long may no longer be effective and could cause generalized hyperarousal.
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