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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice
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Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice

机译：代谢型谷氨酸受体亚型2基因敲除小鼠增强可卡因反应能力和运动协调受损。

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摘要

Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2~(-/-) knockout (KO) mice to explore the physiological role of mGluR2 in brain function. Although, under general observation, mGluR2~(-/-) KO mice appeared to have no behavioral abnormalities, they exhibited several lines of behavioral alterations in the enforcing and defined behavioral tests. They showed a significant increase in locomotor sensi-tization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine. Upon in vivo microdialysis analysis after cocaine administration, not only did extracellular levels of dopa-mine increase but also the response pattern of glutamate release markedly changed in the nucleus accumbens of mGluR2~(-/-) KO mice. The mGluR2~(-/-) KO mice also showed significant impairment in motor coordination in the accelerating rota-rod test and exhibited hyperlocomotion in novel environmental and stressful conditions, when assessed by the open-field and forced-swim tests. These results indicate that the inhibitory mGluR2 plays a pivotal role in synaptic regulation of glutamatergic transmission in the neural network.
机译：最近出现了广泛的药理研究，表明包含mGluR2和mGluR3亚型的第2组代谢型谷氨酸受体（mGluRs）与几种神经系统疾病和精神疾病有关。 mGluR2在突触前和突触后广泛分布在多种神经元细胞中，但人们对mGluR2在脑功能中的生理作用知之甚少。这项研究涉及对mGluR2〜（-/-）敲除（KO）小鼠的综合行为分析，以探讨mGluR2在脑功能中的生理作用。尽管在一般观察下，mGluR2〜（-/-）KO小鼠似乎没有行为异常，但它们在执行和定义的行为测试中表现出几行行为改变。他们显示，与重复施用可卡因有关，运动敏感性和条件性场所偏好显着增加，表明mGluR2有助于涉及可卡因强化和成瘾的行为反应。在给予可卡因后体内微透析分析中，不仅mGluR2〜（-/-）KO小鼠伏隔核中胞外多巴胺水平增加，而且谷氨酸释放的响应模式也明显改变。 mGluR2〜（-/-）KO小鼠在加速旋转棒试验中还显示出运动协调性显着受损，并在新环境和压力条件下表现出超运动性，通过开场试验和强迫游泳试验进行评估。这些结果表明，抑制性mGluR2在神经网络中谷氨酸能传递的突触调节中起关键作用。

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