5-HT1A receptor knockout mice and mice overexpressing corticotropin-releasing hormone in models of anxiety
5-HT1A receptor knockout mice and mice overexpressing corticotropin-releasing hormone in models of anxiety
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DOI：
10.1016/s0014-2999(03)01281-0
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发表时间：
2003-02-28
影响因子：
5
通讯作者：
Olivier, B
中科院分区：
文献类型：
--
作者：
Groenink, L;Pattij, T;Olivier, B
药理学实验暗示了5-羟色胺（5-HT）（1A）受体在焦虑调节中的作用。最近对促肾上腺皮质激素释放激素（CRH）系统作为治疗焦虑症的潜在靶点的兴趣越来越大。然而，针对CRH系统的选择性药理工具有限，阻碍了这一领域的研究。基因靶向是一种相对较新的研究焦虑障碍机制的方法。在三种不同的背景菌株上建立了5-HT1A受体敲除（1AKO）小鼠，并产生了两种不同的过表达cri （CRH-OE）的小鼠系。在本综述中，行为和生理方面的研究结果将报告I AKO小鼠和CRH-OE小鼠。作为行为。表型通常局限于一种或两种方法回避范式，我们扩展了这些观察结果，并在条件恐惧范式中测试了1AKO和CRH-OE小鼠。这种范式反映了焦虑的本质上不同的方面，而不是接近回避范式。129/Sv背景菌株的1AKO小鼠表现出与野生型（WT）小鼠相似的冻结。在CRH-OE小鼠中，观察到的冻结比相应的野生型小鼠少。这些转基因小鼠的焦虑表型似乎不像最初报道的那样清楚，这一事实将被讨论。比起研究靶基因改变的直接后果，1AKO和CRH-OE小鼠似乎对研究基因表达终身变化的代偿过程非常有价值。(C) 2003 Elsevier Science B.V.版权所有
Pharmacological experiments have implicated a role for serotonin (5-HT)(1A) receptors in the modulation of anxiety. More recent is the interest in corticotropin-releasing hormone (CRH) system as a potential target for the treatment of anxiety disorders. However, selective pharmacological tools for the CRH system are limited, hampering research in this field. Gene targeting is a relatively new approach to study mechanisms underlying anxiety disorders. 5-HT1A receptor knockout (1AKO) mice have been created on three different background strains, and two different lines of mice, overexpressing CRI-I (CRH-OE), have been generated. In the present review, behavioural and physiological findings reported for I AKO mice and CRH-OE mice will be reviewed. As behavioural. phenotyping is often limited to one or two approach avoidance paradigms, we extended these observations and also tested 1AKO and CRH-OE mice in a conditioned fear paradigm. This paradigm reflects essentially different aspect of anxiety than approach avoidance paradigms. 1AKO mice on a 129/Sv background strain showed similar freezing as wild-type (WT) mice. In CRH-OE mice, less freezing was observed than in the corresponding wild-type mice. The fact that the anxious phenotype of these genetically altered mice seems less clear than initially reported will be discussed. Rather than studying the direct consequences of alterations in the targeted gene, 1AKO and CRH-OE mice seem very valuable to study compensatory processes that seem to have taken place in reaction to life-long changes in gene expression. (C) 2003 Elsevier Science B.V. All rights reserved.