Reduced stress-induced hyperthermia in mGluR5 knockout mice
Reduced stress-induced hyperthermia in mGluR5 knockout mice
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DOI：
10.1046/j.1460-9568.2002.02294.x
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发表时间：
2002-12-01
影响因子：
3.4
通讯作者：
Varney, MA
中科院分区：
文献类型：
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作者：
Brodkin, J;Bradbury, M;Varney, MA
基于选择性mGluR 5拮抗剂MPEP（2-甲基-6-（苯乙炔基）吡啶）在啮齿动物焦虑模型（包括应激）中的抗焦虑作用，有人认为代谢型谷氨酸受体亚型5（mGluR 5）在焦虑的表达中发挥作用诱导体温过高（SIH）。为了研究mGlu 5受体在焦虑表达中的作用，我们研究了缺乏mGluR 5的小鼠在SIH程序的几种变化中的应激反应。在这种情况下，压力会导致体温轻度升高，这可以被已知的抗焦虑药物阻断。采用了三种程序：使用直肠探针测量体温的经典SIH，以及响应于盐水注射或将入侵者引入饲养笼的体温的无线电遥测测量。在所有三个程序中，与同窝野生型对照小鼠相比，mGluR 5敲除小鼠显示出对应激的高热反应的显著减弱。为了证实我们的观察结果可能是由于mGluR 5在敲除小鼠中的缺失，我们还测试了最近描述的选择性mGluR 5拮抗剂MTEP（3-[（2-甲基-1，3-噻唑-4-基）乙炔基]吡啶）在野生型和mGluR 5敲除小鼠中的作用。在野生型小鼠中施用MTEP，而不是mGluR 5敲除小鼠，减弱了SIH。mGluR 5敲除小鼠表现出抗焦虑样表型，而mGluR 5拮抗剂MTEP仅在具有mGluR 5的小鼠中表现出抗焦虑样作用，这进一步支持了mGluR 5拮抗剂可用于治疗焦虑的建议。
It hs been suggested that metabotropic glutamate receptor subtype 5 (mGluR5) play a role in the expression of anxiety, based on anxiolytic-like effects of the selective mGluR5 antagonist MPEP (2-methyl-6-(phenylethynyl)pyridine) in rodent models of anxiety, including stress-induced hyperthermia (SIH). To examine the suggested role of mGlu5 receptors in the expression of anxiety, we examined the stress response in mice lacking mGluR5 in several variations of the SIH procedure. In this paradigm, stress causes a mild increase in body temperature that can be blocked by known anxiolytic agents. Three procedures were employed: classical SIH using rectal-probe measurement of body temperature, and radiotelemetric measurement of body temperature in response to either saline injection or to the introduction of an intruder into the home cage. In all three procedures the mGluR5-knockout mice displayed a significant attenuation of the hyperthermic response to stress compared to littermate wild-type control mice. To confirm that our observations were likely to be due to the absence of mGluR5 in the knockout mice we also tested the effect of the recently described selective mGluR5 antagonist MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine) in both the wild-type and mGluR5 knockout mice. Administration of MTEP in the wild-type mice, but not the mGluR5 knockout mice, attenuated SIH. That the mGluR5 knockout mice displayed an anxiolytic-like phenotype and that the mGluR5 antagonist, MTEP, showed a anxiolytic-like effect only in mice possessing mGluR5 further supports the suggestion that mGluR5 antagonists may be useful in the treatment of anxiety.