内侧前额叶前边缘皮层在应激诱发的时间依赖性恐惧焦虑行为中的作用研究

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	内侧前额叶前边缘皮层在应激诱发的时间依赖性恐惧焦虑行为中的作用研究
其他题名	Role of prelimbic medical prefrontal cortex in time-dependent stress-induced anxiety and fear
	张丽丽
	2015-05
摘要	近年来，随着地震、海啸、恐怖袭击等创伤性事件频频发生，创伤后应激障碍（poaumatic stress disorder, PTSD）越来越受到研究者的关注。PTSD 是指由于异常威胁性或灾难性心理创伤导致延迟出现和长期持续的精神障碍。临床上，创伤后应激障碍表状在经历创伤后至少 6 个月才首次爆发。与其他应激相关障碍相比较，延迟发作是创伤后应激障碍所独有的特点。对于创伤后应激障碍的延迟发作，大量的研究集中于 startle 的行为研究。部分研究集中于条件性恐惧孵育的研究，然而对于非条件性恐惧及其焦虑行为的研究较少。因此，本研究中，我们想考察延迟发作的应激相关症状（即时间依赖性恐惧与焦虑行为）与应激强度存在什么样的关系？进而建立时间依赖的恐惧焦虑行为模型。已有研究表明，内侧前额叶皮层的前边缘皮层（prelimbic cortex, PL）参与恐惧与焦虑行为的调节。此外，条件性恐惧的研究表明内侧前额叶皮层前边缘区参与恐惧记忆的调节。那么在应激所导致的时间依赖的恐惧焦虑行为改变中，PL 是否参与着这个时间孵育的过程？如果参与，那么它又发挥着什么样的作用呢？恐惧消退是创伤记忆的有效干预方式，已有研究表明，单次恐惧消退和重复多次恐惧消退对于恐惧行为的效果不同。单次恐惧消退近期可以显著的降低恐惧，但是远期会有恐惧的复发，而重复多次的恐惧消退可以有效的防止恐惧复发。基于此，本课题从以下两个方面进行研究 1. 建立应激诱发的时间依赖性行为模型 2. 在此模型的基础上，通过免疫荧光和神经药理学的方法检测 PL 区在时间孵育过程中的作用。 3. 采用单次消退和重复多次消退，探索恐惧记忆与时间依赖的恐惧和焦虑行为的关系。研究结果如下： 1. 高强度的应激会导致时间依赖性的非条件性恐惧与焦虑行为。 2. 高强度应激所导致的非条件的恐惧与焦虑行为中，PL 激活存在差异。非条件恐惧行为改变与 PL 的活性改变一致，提示 PL 可能参与非条件恐惧行为的调节；而焦虑行为的改变与 PL 活性改变并不一致。提示 PL 可能并不直接参与焦虑行为随时间改变的调节。 3. 药理性失活 PL，会导致非条件性恐惧行为的增加，但是药理性失活 PL，并不会影响近期的焦虑行为，但是会导致远期焦虑行为降低。提示：PL 参与非条件恐惧行为的时间孵育过程，而对于焦虑行为的调节可能通过间接调节的方式来实现。 4. 单次情景恐惧消退和连续三次情景恐惧消退（总消退时间相同）对于非条件性恐惧行为和焦虑行为的影响不同。单次消退在情景恐惧复发的同时，依旧显著的降低了非条件的恐惧行为，却并没有显著的影响焦虑行为，同时也并不伴随 PLc-fos 表达的显著改变。连续三次消退的消退方式能够有效的降低情景性恐惧的同时，显著的降低了焦虑行为，同时伴随着 PLc-fos 表达的显著改变，而并不能显著的改变非条件性恐惧行为。结果提示：焦虑行为随时间改变的过程可能与恐惧记忆相关，PL对于焦虑行为的调节可能依赖于条件性恐惧记忆。
其他摘要	In recent years, post-traumatic stress disorder (PTSD) was more and more attentioned by researchers along with the frequent earthquakes, tsunamis, terrorist attacks and other traumatic events. PTSD was a delayed and long-lasting mental disorder because of abnormal threatening or catastrophic psychological trauma. Symptoms of PTSD first erupted at least 6 months after trauma, which was defined as delayed onset PTSD (DPTSD). Delay onset was one of important features of PTSD. a large number of studies related to DPTSD had focused on startle and conditionning fear incubation , but few studies focused on anxiety behavior. Therefore, in our research, we hoped to investigate the relationship between time-dependent fear and anxiety behavior and stress intesity，and establish animal model of a time-dependent fear and anxiety. In addition, many studies suggestted that the prelimbic medial prefrontal cortex (PL) involved in the regulation of fear, anxiety behavior and fear memory. But there is no research about the effect of PL in time dependent fear and anxiety. So, in our research, we investigated the role of PL in time-dependent dependent fear and anxiety. Fear extinction was an effective intervention for traumatic memories, many studies had suggested that single fear extinction reduced fear in recent and relapsed in remote. But repeatly extinction not only significantly reduced fear in recent, but also prevented fear replapse. Therefore, this study contains two aspects of research： 1. Establish a stress-induced time-dependent behavior model 2. Based on this animal model, investigate the role of PL in time dependent fear and anxiety by immunofluorescence and neuropharmacology techniques. 3. To investigate the relationship between fear memory and time-dependent fear and anxiety behaviour. Our results are as follows: 1. Strong stress can lead to time-dependent unconditional fear and anxiety behavior . 2. There was difference in number of c-fos positive cell in PL cortex between strong stress induced unconditional Fear and anxiety behavior. There was consistent change between the fear in novel environment and number of PL c-fos positive cell. This suggestted that PL may be involved in regulating fear in novel environment. Meanwhile, the change of anxiety behaviour in EPM test was inconsistent with the change of number of PL c-fos positive cell. This may be due to the PL not directly involved in the regulation of EPM. 3. Inactivation PL lead to increase in fear in novel environment test and lower anxiety in EPM test. This suggestted that the PL may be involved in the regulation of fear in novel environment but not in anxiety behavior in EPM test. 4. Two different extinctions resulted in different influence between fear in novel environment test and anxiety in EPM test. Single contextual fear extinction reduced the fear in novel environment and no effect in the anxiety in EPM test , accompaning by the context fear relapse and significant changes in PL activity. Three consecutive extinction can significantly reduce context fear and anxiety in EPM test, accompaning with a significant change in PL activity. But it did not significantly change fear in novel environment test. This suggested that PL regulated anxious behavior dependent on conditioned fear memory. But the regulation of fear in novel environment was indenpent in the conditioned fear momery.
学科领域	医学心理学
关键词	创伤后应激障碍时间依赖性恐惧焦虑恐惧消退前边缘皮层
学位类型	博士
语种	中文
学位专业	心理学
学位授予单位	中国科学院研究生院
学位授予地点	北京
文献类型	学位论文
条目标识符	http://ir.psych.ac.cn/handle/311026/19760
专题	健康与遗传心理学研究室
作者单位	中国科学院心理研究所
推荐引用方式 GB/T 7714	张丽丽. 内侧前额叶前边缘皮层在应激诱发的时间依赖性恐惧焦虑行为中的作用研究[D]. 北京. 中国科学院研究生院,2015.

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