Reinstatement of extinguished fear by an unextinguished conditional stimulus
Reinstatement of extinguished fear by an unextinguished conditional stimulus
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DOI：
10.3389/fnbeh.2012.00018
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发表时间：
2012-05-04
影响因子：
3
通讯作者：
Fanselow, Michael S.
中科院分区：
文献类型：
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作者：
Halladay, Lindsay R.;Zelikowsky, Moriel;Fanselow, Michael S.
焦虑障碍通常使用基于消除的暴露疗法进行治疗，但复发是常见的，并且可能作为恢复的结果发生，即厌恶的“触发因素”可以恢复被消除的恐惧。动物复原模型通常使用巴甫洛夫恐惧条件反射程序，在该程序中，受试者首先通过将条件刺激（CS）与厌恶的无条件刺激（US）配对来训练对其产生恐惧，然后通过反复呈现单独的CS来消除。恢复通常是通过将受试者暴露于灭绝后的厌恶美国而引起的，但在这里，我们发现暴露于未熄灭的CS可以恢复对熄灭CS的条件恐惧，我们将这种现象称为“条件恢复”（CRI）。大鼠被训练成害怕两种CS（光和色调），随后又接受了只害怕一种CS（平衡）的灭绝训练。在消失后立即呈现未消失的CS（但不是新的线索），在24小时后的测试中恢复了对消失CS的条件恐惧反应。这些发现表明，暴露于有条件的和无条件的厌恶刺激都可以触发被消除的恐惧的恢复，这可能有助于解释为什么临床消除治疗后复发在人类中很常见。使用动物模型对CRI进行进一步研究可能有助于开发更能抵抗恢复的精细灭绝疗法。
Anxiety disorders are often treated using extinction-based exposure therapy, but relapse is common and can occur as a result of reinstatement, whereby an aversive "trigger" can reinstate extinguished fear. Animal models of reinstatement commonly utilize a Pavlovian fear conditioning procedure, in which subjects are first trained to fear a conditional stimulus (CS) by pairing it with an aversive unconditional stimulus (US), and then extinguished by repeated presentations of the CS alone. Reinstatement is typically induced by exposing subjects to an aversive US after extinction, but here we show that exposure to a non-extinguished CS can reinstate conditional fear responding to an extinguished CS, a phenomenon we refer to as "conditional reinstatement" (CRI). Rats were trained to fear two CSs (light and tone) and subsequently underwent extinction training to only one CS (counterbalanced). Presenting the unextinguished CS (but not a novel cue) immediately after extinction reinstated conditional fear responding to the extinguished CS in a test session given 24 h later. These findings indicate that reinstatement of extinguished fear can be triggered by exposure to conditional as well as unconditional aversive stimuli, and this may help to explain why relapse is common following clinical extinction therapy in humans. Further study of CRI using animal models may prove useful for developing refined extinction therapies that are more resistant to reinstatement.