The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia
The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia
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DOI：
10.1016/j.expneurol.2010.09.008
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发表时间：
2011-01-01
影响因子：
5.3
通讯作者：
Gass, Peter
中科院分区：
文献类型：
--
作者：
Ben Abdallah, Nada M-B;Fuss, Johannes;Gass, Peter
执行功能缺陷是精神分裂症的主要特征。迄今为止，用于寻找此类缺陷的动物相关性的啮齿动物行为范式需要大量的努力和时间。谜盒是一项解决问题的测试，要求小鼠在有限的时间内完成难度逐渐增加的逃脱任务。先前的数据表明，这是一种快速但高度可靠的高阶认知功能测试。我们评估了使用拼图盒来探索五种不同精神分裂症小鼠模型的执行功能：前额皮质和海马损伤的小鼠、用 NMDA 受体拮抗剂 MK-801 亚慢性治疗的小鼠、组成性缺乏 AMPA 受体 GluA1 亚基的小鼠以及过度表达多巴胺 D2 的小鼠纹状体中的受体。尽管不同模型之间缺陷的性质和程度有所不同，但所有小鼠在拼图盒中都表现出改变的执行功能。海马体损伤和 GluA1 敲除小鼠的缺陷最为明显，而内侧前额叶损伤的小鼠、MK-801 处理的小鼠以及纹状体 D2 受体过度表达的小鼠中发现了更微妙但特定于解决问题的缺陷。 这项研究的数据表明，拼图盒作为一般执行功能（特别是精神分裂症小鼠模型）的有效筛选工具具有实用性。由爱思唯尔公司出版
Deficits in executive functions are key features of schizophrenia. Rodent behavioral paradigms used so far to find animal correlates of such deficits require extensive effort and time. The puzzle box is a problem-solving test in which mice are required to complete escape tasks of increasing difficulty within a limited amount of time. Previous data have indicated that it is a quick but highly reliable test of higher-order cognitive functioning.We evaluated the use of the puzzle box to explore executive functioning in five different mouse models of schizophrenia: mice with prefrontal cortex and hippocampus lesions, mice treated sub-chronically with the NMDA-receptor antagonist MK-801, mice constitutively lacking the GluA1 subunit of AMPA-receptors, and mice over-expressing dopamine D2 receptors in the striatum. All mice displayed altered executive functions in the puzzle box, although the nature and extent of the deficits varied between the different models. Deficits were strongest in hippocampus-lesioned and GluA1 knockout mice, while more subtle deficits but specific to problem solving were found in the medial prefrontal-lesioned mice, MK-801-treated mice, and in mice with striatal overexpression of D2 receptors.Data from this study demonstrate the utility of the puzzle box as an effective screening tool for executive functions in general and for schizophrenia mouse models in particular. Published by Elsevier Inc.