5-HT1A receptor knockout mouse as a genetic model of anxiety.
5-HT1A receptor knockout mouse as a genetic model of anxiety.
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DOI：
10.1016/s0014-2999(03)01280-9
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发表时间：
2003-02
影响因子：
5
通讯作者：
M. Toth
中科院分区：
文献类型：
--
作者：
M. Toth
在情绪和焦虑障碍中反复发现血清素 1A(5-HT1A) 受体水平低。压力常常会加剧精神疾病，还会降低 5-HT1A 受体水平。当通过基因敲除使小鼠产生受体缺陷时，会观察到类似焦虑的表型。小鼠的焦虑被定义为高度回避新的和不熟悉的环境以及增加的恐惧反应。受体敲除小鼠中也描述了焦虑的其他方面，例如自主神经激活、应激反应性增加和神经内分泌异常。这些数据表明，5-HT1A 受体敲除小鼠代表了具有结构和表面有效性的焦虑遗传动物模型。尽管焦虑的核心表型可以在各种近交和远交背景的基因敲除小鼠中重现，但 5-HT 动力学异常和抗焦虑药物地西泮抗性在其中一种小鼠中出现，但在其他遗传背景中却没有出现。这表明虽然焦虑的发展是受体缺陷的必然结果，但受体缺失引起的其他特征受到其他基因的强烈调节。核心表型内的品系依赖性变异并不会降低 5-HT1A 受体敲除小鼠作为焦虑模型的价值。事实上，这与遗传异质人群中焦虑的表现是一致的。
Low levels of the serotonin1A(5-HT1A) receptor have been repeatedly found in mood and anxiety disorders. Stress often exacerbates psychiatric disease and can also reduce 5-HT1Areceptor levels. When receptor deficiency was produced in mice by genetic knockout, an anxiety-like phenotype was observed. Anxiety in mice is defined as a high level of avoidance of novel and unfamiliar environment and increased fear reaction. Other aspects of anxiety such as autonomic activation, increased stress responsiveness, and neuroendocrine abnormalities have also been described in receptor knockout mice. These data indicate that 5-HT1Areceptor knockout mice represent a genetic animal model of anxiety with both construct and face validities. Although the core phenotype of anxiety can be reproduced in knockout mice in various inbred and outbred backgrounds, abnormalities in 5-HT dynamics and resistance to the anxiolitic drug diazepam have been seen in one but not on other genetic backgrounds. This indicates that while the development of anxiety is an invariable consequence of receptor deficit, other features induced by receptor loss are strongly modulated by other gene(s). Strain-dependent variability within the core phenotype does not diminish the value of 5-HT1Areceptor knockout mice as a model of anxiety. Indeed, it is consistent with the manifestation of anxiety in genetically heterogeneous human population.