Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder
Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder
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DOI：
10.1016/j.physbeh.2011.08.037
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发表时间：
2012-01-18
影响因子：
2.9
通讯作者：
Takahashi, Lorey K.
中科院分区：
文献类型：
--
作者：
Corley, Michael J.;Caruso, Michael J.;Takahashi, Lorey K.
创伤后应激障碍（PTSD）的特征是应激诱导的症状，包括夸大的恐惧记忆，过度警觉和过度觉醒。然而，我们不知道一个动物模型，研究这些特征的创伤后应激障碍，特别是与恐惧消退和习惯化。因此，开发一个有效的创伤后应激障碍的动物模型，我们将大鼠暴露于不同强度的足电击应激，以确定其对听觉捕食者气味恐惧消退或习惯化的恐惧敏感化的影响。在实验1中，大鼠暴露于急性footshock应激（无休克控制，0.4 mA，或0.8 mA）听觉恐惧条件反射训练之前，涉及配对的听觉点击与含有猫气味的布。当呈现条件性听觉点击在未来5天的消光测试进行的跑道装置与隐藏盒，大鼠在两个休克组从事更高水平的冻结和头出警戒样行为的隐藏盒比无休克对照组。这种增加的恐惧行为在灭绝测试可能是由于听觉激活的条件恐惧状态，因为实验2表明，条件恐惧行为并没有广泛增加条件听觉刺激的情况下。然后进行实验3，以确定急性暴露于压力是否会诱导习惯化抗性敏化恐惧状态。我们发现，大鼠暴露于0.8 mA的footshock应力，随后测试了5天的跑道隐藏盒装置与非联想听觉点击呈现高初始水平的冻结，随后由头出的行为，并最终在运动功能亢进的发生。此外，实验4表明，没有交付的非联想听觉点击，0.8 mA的脚电击应激大鼠并没有表现出强烈的增加，敏化冻结和运动过度活跃，虽然头出警戒样行为继续观察。总之。我们的动物模型提供了关于不同强度的足电击应激、捕食者-捕食者气味恐惧条件反射以及它们的相互作用对促进抵抗性恐惧或抵抗性习惯性恐惧相关行为的影响的新信息。这些结果为令人兴奋的PTSD特征的新研究奠定了基础，这些特征包括压力诱导的创伤记忆和敏感恐惧的形成和持续。(C)2011 Elsevier Inc. All rights reserved.
Posttraumatic stress disorder (PTSD) is characterized by stress-induced symptoms including exaggerated fear memories, hypervigilance and hyperarousal. However, we are unaware of an animal model that investigates these hallmarks of PTSD especially in relation to fear extinction and habituation. Therefore, to develop a valid animal model of PTSD, we exposed rats to different intensities of footshock stress to determine their effects on either auditory predator odor fear extinction or habituation of fear sensitization. In Experiment 1, rats were exposed to acute footshock stress (no shock control, 0.4 mA, or 0.8 mA) immediately prior to auditory fear conditioning training involving the pairing of auditory clicks with a cloth containing cat odor. When presented to the conditioned auditory clicks in the next 5 days of extinction testing conducted in a runway apparatus with a hide box, rats in the two shock groups engaged in higher levels of freezing and head out vigilance-like behavior from the hide box than the no shock control group. This increase in fear behavior during extinction testing was likely due to auditory activation of the conditioned fear state because Experiment 2 demonstrated that conditioned fear behavior was not broadly increased in the absence of the conditioned auditory stimulus. Experiment 3 was then conducted to determine whether acute exposure to stress induces a habituation resistant sensitized fear state. We found that rats exposed to 0.8 mA footshock stress and subsequently tested for 5 days in the runway hide box apparatus with presentations of nonassociative auditory clicks exhibited high initial levels of freezing, followed by head out behavior and culminating in the occurrence of locomotor hyperactivity. In addition, Experiment 4 indicated that without delivery of nonassociative auditory clicks, 0.8 mA footshock stressed rats did not exhibit robust increases in sensitized freezing and locomotor hyperactivity, albeit head out vigilance-like behavior continued to be observed. In summary. our animal model provides novel information on the effects of different intensities of footshock stress, auditory-predator odor fear conditioning, and their interactions on facilitating either extinction-resistant or habituation-resistant fear-related behavior. These results lay the foundation for exciting new investigations of the hallmarks of PTSD that include the stress-induced formation and persistence of traumatic memories and sensitized fear. (C) 2011 Elsevier Inc. All rights reserved.