Optimization of chronic stress paradigms using anxiety- and depression-like behavioral parameters
Optimization of chronic stress paradigms using anxiety- and depression-like behavioral parameters
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DOI：
10.1002/jnr.20754
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发表时间：
2006-02-15
影响因子：
4.2
通讯作者：
Han, PL
中科院分区：
文献类型：
--
作者：
Kim, KS;Han, PL
慢性压力是精神疾病的风险因素，如焦虑和抑郁症。为了理解慢性压力如何引发精神功能障碍的潜在机制，过去已经尝试了基于约束的慢性压力模型。然而，重复约束应力的总持续时间和最后一次约束应用后使用的评估时间点因实验而异。这些方法异质性的一个原因与慢性应激的定义相当模糊有关，特别是在动物模型中。在本研究中，我们使用行为特征、焦虑和抑郁作为压力评估参数，以满足对慢性压力状态定义的操作有用要求。我们证明，连续14天每天2或8小时的约束治疗足以产生类似焦虑和抑郁的行为，而2小时至10天的约束治疗效果甚微。基因芯片分析发现，海马区34个基因和杏仁核区72个基因的表达水平被>上调或下调2.0倍。在该分析中鉴定的广泛基因中，能量代谢、信号转导、转录、突触可塑性和脑结构重塑所需的基因是值得注意的。我们的研究结果表明，焦虑和抑郁的精神病学标准可以作为慢性压力评估参数，并且由每天2或8小时的约束治疗组成的约束压力范式可以作为慢性压力研究的原型范式。(c) 2006 Wiley-Liss, Inc。
Chronic stress is a risk factor for psychiatric illnesses, such as anxiety and depression disorders. To understand the underlying mechanism regarding how chronic stress triggers such psychiatric dysfunctions, restraint-based chronic stress models have been attempted in the past. However, total durations of repeated restraint stress and the evaluation time points used after the last restraint application vary from experiment to experiment. One reason for these methodological heterogeneities is related to considerable ambiguity concerning the definition of chronic stress, particularly in animal models. In the present study, we used behavioral traits, anxiety and depression, as stress-assessment parameters that meet operationally useful requirements for the definition of the chronic stress state. We demonstrate that restraint treatment for 2 or 8 hr daily for 14 days is enough to produce anxiety- and depression-like behaviors, whereas a 2 hr-10 days restraint was marginally effective. cDNA microarray analysis identified 34 genes in the hippocampus and 72 genes in the amygdala with expression levels that were up- or down-regulated by > 2.0-fold. Among the wide range of genes identified in this analysis, genes required for energy metabolism, signal transduction, transcription, synaptic plasticity, and remodeling of the brain architecture were notable. Our results suggest that the psychiatric criteria of anxiety and depression can be used as chronic stress-assessment parameters and that a restraint stress paradigm consisting of restraint treatment for 2 or 8 hr daily for 14 days could be used as a prototype paradigm for chronic stress studies. (c) 2006 Wiley-Liss, Inc.