OSO PARADIGM - A RAPID BEHAVIORAL SCREENING METHOD FOR ACUTE PSYCHOSOCIAL STRESS REACTIVITY IN MICE
OSO PARADIGM - A RAPID BEHAVIORAL SCREENING METHOD FOR ACUTE PSYCHOSOCIAL STRESS REACTIVITY IN MICE
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DOI：
10.1016/j.neuroscience.2015.11.043
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发表时间：
2016-02-09
期刊：
影响因子：
3.3
通讯作者：
Rossner, M. J.
中科院分区：
文献类型：
--
作者：
Brzozka, M. M.;Unterbarnscheidt, T.;Rossner, M. J.
慢性心理社会应激是精神疾病发展的重要环境危险因素。然而，研究慢性心理社会压力对小鼠的影响是耗时的，因此不适合“筛选”越来越多的遗传操纵小鼠模型的精神病内表型。此外，许多研究集中在约束压力，一个强大的身体压力源与精神疾病的相关性有限。在这里，我们描述了一个简单而快速的方法的基础上的居民入侵者的范例，以检查小鼠轻度心理社会应激的急性影响。OSO范式（旷场-社交失败-旷场）比较了暴露于急性社交失败压力之前和之后对运动活动、焦虑和好奇心的行为后果。我们首先在雄性C57 BI/6野生型小鼠中评估了OSO，其中单次社交失败减少了运动活动，增加了焦虑和减少了探索行为。随后，我们应用OSO范式的两个精神分裂症（SZ）的风险基因的小鼠模型。神经元过度表达Neuregulin-1（Nrg 1）III型的转基因小鼠在急性应激暴露后表现出增加的冒险行为，这表明NRG 1功能障碍与情感行为改变有关。相反，Tcf 4转基因小鼠显示正常的应激反应，这与TCF 4对SZ认知缺陷的假定主要贡献一致。总之，OSO范式允许在精神疾病小鼠模型中快速筛选选定的心理社会应激诱导的行为内表型。(C)2015年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Chronic psychosocial stress is an important environmental risk factor for the development of psychiatric diseases. However, studying the impact of chronic psychosocial stress in mice is time consuming and thus not optimally suited to 'screen' increasing numbers of genetically manipulated mouse models for psychiatric endophenotypes. Moreover, many studies focus on restraint stress, a strong physical stressor with limited relevance for psychiatric disorders. Here, we describe a simple and a rapid method based on the resident-intruder paradigm to examine acute effects of mild psychosocial stress in mice. The OSO paradigm (open field - social defeat - open field) compares behavioral consequences on locomotor activity, anxiety and curiosity before and after exposure to acute social defeat stress. We first evaluated OSO in male C57BI/6 wildtype mice where a single episode of social defeat reduced locomotor activity, increased anxiety and diminished exploratory behavior. Subsequently, we applied the OSO paradigm to mouse models of two schizophrenia (SZ) risk genes. Transgenic mice with neuronal overexpression of Neuregulin-1 (Nrg1) type III showed increased risk-taking behavior after acute stress exposure suggesting that NRG1 dysfunction is associated with altered affective behavior. In contrast, Tcf4 transgenic mice displayed a normal stress response which is in line with the postulated predominant contribution of TCF4 to cognitive deficits of SZ. In conclusion, the OSO paradigm allows for rapid screening of selected psychosocial stress-induced behavioral endophenotypes in mouse models of psychiatric diseases. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.