大鼠恐惧与焦虑行为的分离—来自行为与药理学的证据

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	大鼠恐惧与焦虑行为的分离—来自行为与药理学的证据
其他题名	Dissociations between fear and anxiety behaviors: Evidence from studies of behavior and pharmacology
	王红波
	2014-05
摘要	以消退为基本原理的暴露疗法是临床上治疗焦虑障碍最有效的方法，但治疗后的高比例复发是一个严重问题。焦虑障碍以过度恐惧和持久焦虑为特征。虽然恐惧和焦虑很相似，但近十年已不断有研究报道恐惧和焦虑在多个维度上都是不同的。因为恐惧和焦虑有功能上的异质性，并涉及到不同的神经和心理药理机制，所以需要用独立的方法来治疗。然而，至今为止，对暴露疗法治疗后的复发主要是恐惧症状还是焦虑症状知之甚少。在前临床研究中，恐惧和焦虑的不同至少体现在两个维度上：引发行为的刺激的持续时间量（瞬间还是持久）和危险的性质（可预测的还是不可预测的）。基于消退后条件信号的预测性降低，预示危险的意义变得不确定，我们假设复发更类似于一种“焦虑”状态。对此，本研究采用最典型的大鼠恐惧复发模型-续新，进行了一系列实验探索。首先从行为层面探索续新对焦虑样行为的影响，随后探索主要参与焦虑而不参与恐惧的脑结构-终纹床核（BNST）在续新中的作用，最后探索具有抗焦虑效应的皮质酮对续新的影响。研究发现：（1）消退可以明显降低应激诱发的焦虑，但消退对焦虑的影响是脆弱的，可以被续新阻断。续新后动物的焦虑水平甚至会显著高于未经消退的应激动物，提示续新的致焦虑效应可能更强。（2）暂时性失活 BNST可以降低消退后的续新而不影响消退前的恐惧表达，表明恐惧续新和恐惧表达涉及到不同的神经环路，提示续新可能是一种焦虑。（3）应激后立即（1h）和延迟（24h）的高剂量皮质酮干预会减少大鼠 EPM 焦虑样行为，但不损害大鼠线索和情境恐惧记忆的表达，这表明应激后皮质酮不损害恐惧记忆的巩固和提取，但具有抗焦虑效应。（4）应激后立即（1h）和延迟（24h）的高剂量皮质酮干预在不影响恐惧记忆和消退记忆的情况下选择性地降低恐惧续新，提示皮质酮可能是通过抗焦虑效应降低续新。基于续新中条件刺激预示危险的意义不明确，综合以上这些结果，我们提出消退后条件刺激引发的恐惧续新与消退前条件刺激引发的恐惧表达是两种不同的状态：消退前条件刺激引起的恐惧表达是一种“恐惧”状态，而消退后条件刺激诱发的恐惧续新更类似于一种“焦虑”状态。
其他摘要	Abstract Exposure therapy based on extinction is one of the most effective treatments for anxiety disorders. However, relapse or the return of fear presents a significant problem for the treatment after exposure-based therapies. Anxiety disorders are characterized by excessive fear and sustained anxiety. Although the physical and psychological manifestations of anxiety and fear appear to share commonalities, there is now substantial evidence to suggest that fear and anxiety can also be differentiated at several dimensions. Because fear and anxiety are functionally heterogeneous, reflecting involvement of distinct underlying neural and psychopharmacology mechanisms, they can be treated with independent therapeutic strategies. However, which aversive state is predominant in relapse remains unclear. In preclinical studies, fear and anxiety differ in at least two dimensions: their duration (phasic versus sustained) and the nature of the threat (predictable versus unpredictable). Given that the conditioned stimulus (CS) is less predictable and less spcific after entinction, we hypothesized that relapse of fear is akin to “anxiety” state. In the present study, a typical renewal paradigm was usd, in which a rodent presented with an extinguished stimulus in a context that is different than the extinction context will show a renewal of the original fear response. First, we examined the effect of fear renewal on anxiety-like behavior in the elevated plus maze (EPM). Then, we explored the role of the bed nucleus of the stria terminalis (BNST) in fear reneal. Last, we investigated the effect of corticosterone on renewal. The main findings are described as belows: 1. Extinction decreased stress-induced anxiety, however, the anxiolytic effect of extinction was blocked by renewal. And renewal might exacerbate the anxiogenic effect of stress. 2. Inactivation of the BNST suppressed fear renewal but not fear expression. 3. High-dose corticosterone after fear conditioning selectively reduced anxiety-like behavior in the EPM, but had no effect on consolidation and retrieval of fear memory. 4. High-dose corticosterone after fear conditioning selectively reduced fear renewal without facilitating consolidation of extinction memory. Base on the uncertainty of CS and these results, it is proposed that the CS-elicited aversive states during fear expression and fear renewal might be associated with “fear” and “anxiety”, respectively.
学科领域	医学心理学
关键词	条件性恐惧消退续新焦虑终纹床核糖皮质激素
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/311026/19708
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	王红波. 大鼠恐惧与焦虑行为的分离—来自行为与药理学的证据[D]. 北京. 中国科学院研究生院,2014.

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