Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor

Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor
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DOI:
10.1016/s0028-3908(02)00079-5
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发表时间:
2002-08-01
期刊:
影响因子:
4.7
通讯作者:
Schoepp, DD
Schoepp, DD
中科院分区:
医学2区
文献类型:
--
作者:
Linden, AM;Johnson, BG;Schoepp, DD

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突触前代谢型谷氨酸(mGlu)受体通过控制谷氨酸和γ-氨基丁酸(GABA)的释放来调节神经元的兴奋性。mGlu 8受体主要存在于突触前末梢,其表达受到高度限制。为了研究这种受体的作用,产生了mGlu 8受体缺陷小鼠。在这里,我们报告说,幼稚mGlu 8受体缺陷小鼠表现出增加焦虑相关的行为,在高架十字迷宫在低照明条件下(红光)。突变小鼠的开臂回避和风险评估行为均显著增加。增加压力的测试条件取消了这种行为差异。荧光灯或先前的束缚应激降低了野生型小鼠的开臂活动,而突变小鼠的开臂活动基本上不受影响,导致两种品系的值相似。臂进入或闭合臂进入的总数在品系之间没有显著差异,表明缺乏mGlu 8受体不影响运动活性。在突变小鼠中未观察到大体行为变化或自主神经系统或躯体运动系统功能的变化。此外,没有显着差异,在癫痫发作的敏感性检测菌株之间。我们的研究结果表明,mGlu 8受体可能在新的应激环境的反应中发挥作用。(C)2002爱思唯尔科技有限公司版权所有。
Pre-synaptic metabotropic glutamate (mGlu) receptors modulate neuronal excitability by controlling glutamate and gamma-aminobutyric acid (GABA) release. The mGlu8 receptor is predominantly found in pre-synaptic terminals and its expression is highly restricted. To study the role of this receptor, mGlu8 receptor-deficient mice were generated. Here we report that naive mGlu8 receptor-deficient mice showed increased anxiety-related behavior in the elevated plus maze in low illumination conditions (red light). Open arm avoidance and risk assessment behavior were both significantly increased in mutant mice. Increased stressfulness of the testing conditions abolished this behavioral difference. Fluorescent light or prior restraint stress decreased the open arm activity of wild-type mice, while the open arm activity of mutant mice was essentially unaffected, leading to similar values in both strains. The total number of arm entries or closed arm entries was not significantly different between strains, indicating that the lack of mGlu8 receptor does not affect locomotor activity. No gross behavioral changes, or changes in the function of the autonomic nervous system or somatomotor systems were observed in mutant mice. Moreover, no significant differences in seizure susceptibility were detected between strains. Our results suggest that mGlu8 receptor may play a role in responses to novel stressful environment. (C) 2002 Elsevier Science Ltd. All rights reserved.