Toth Miklos
Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, LC 522, New York, NY 10021, USA.
Eur J Pharmacol. 2003 Feb 28;463(1-3):177-84. doi: 10.1016/s0014-2999(03)01280-9.
Low levels of the serotonin(1A) (5-HT(1A)) receptor have been repeatedly found in mood and anxiety disorders. Stress often exacerbates psychiatric disease and can also reduce 5-HT(1A) receptor 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-HT(1A) receptor 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-HT(1A) receptor knockout mice as a model of anxiety. Indeed, it is consistent with the manifestation of anxiety in genetically heterogeneous human population.
血清素（1A）（5-HT（1A））受体水平低下在情绪和焦虑症中屡有发现。应激常常会加重精神疾病，还会降低5-HT（1A）受体水平。通过基因敲除在小鼠中制造受体缺陷时，会观察到类似焦虑的表型。小鼠的焦虑被定义为对新奇和陌生环境的高度回避以及恐惧反应增加。受体敲除小鼠中也描述了焦虑的其他方面，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-HT（1A）受体敲除小鼠代表了一种具有结构效度和表面效度的焦虑基因动物模型。尽管在各种近交和远交背景的敲除小鼠中都能重现焦虑的核心表型，但在一种而非其他基因背景中观察到了5-HT动力学异常和对抗焦虑药物地西泮的耐药性。这表明，虽然焦虑的发展是受体缺陷的必然结果，但受体缺失诱导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性并不降低5-HT（1A）受体敲除小鼠作为焦虑模型的价值。事实上，这与遗传异质性人群中焦虑的表现是一致的。
