Increased binding of cortical and hippocampal group II metabotropic glutamate receptors in isolation-reared mice
Increased binding of cortical and hippocampal group II metabotropic glutamate receptors in isolation-reared mice
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DOI：
10.1016/j.neuropharm.2010.10.009
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发表时间：
2011-02-01
影响因子：
4.7
通讯作者：
Matsuda, Toshio
中科院分区：
文献类型：
--
作者：
Kawasaki, Toshiyuki;Ago, Yukio;Matsuda, Toshio
啮齿动物断奶后的社会隔离会引起行为改变，包括过度运动、抑郁和焦虑样行为、攻击以及学习和记忆缺陷。这些行为异常可能与精神分裂症和抑郁症等神经精神障碍患者的核心症状有关。鉴于近年来有研究表明II组代谢型谷氨酸受体（mGluR2/3）参与神经精神疾病，本研究采用体外放射自显影法研究了分离饲养对小鼠脑内mGluR2/3拮抗剂[H-3]LY341495与mGluR2/3结合的影响。社会隔离饲养显著增加了[H-3]LY341495在前额叶皮层、大脑皮层I-III层和海马区的结合，而在大脑其他区域的结合没有改变。分离饲养小鼠海马膜的饱和结合研究显示，B-max值显著增加，但K-d值没有变化。此外，mGluR2/3拮抗剂MGS0039 （1.0 mg/kg，腹腔注射）在强迫游泳试验中减少了隔离饲养小鼠的静止时间。上述结果提示，隔离饲养引起小鼠前额叶皮层和海马中mGluR2/3密度的增加，受体功能的增加可能参与了隔离饲养小鼠抑郁样行为的致病机制。(C) 2010 Elsevier Ltd.版权所有。
Post-weaning social isolation in rodents induces behavioral alterations, including hyperlocomotion, depression- and anxiety-like behaviors, aggression, and learning and memory deficits. These behavioral abnormalities may be related to the core symptoms in patients with neuropsychiatric disorders, such as schizophrenia and depression. In view of the recent studies that the group II metabotropic glutamate receptor (mGluR2/3) is involved in neuropsychiatric disorders, the present study examined the effect of isolation rearing on the binding of the mGluR2/3 antagonist [H-3]LY341495 to mGluR2/3 in the mouse brain by in vitro autoradiography. The [H-3]LY341495 binding in the prefrontal cortex, cerebral cortical layers I-III and hippocampus was significantly increased by rearing in social isolation while the binding in other brain regions was not altered. A saturation binding study of hippocampal membranes from isolation-reared mice revealed that the B-max value increased significantly without any changes in the K-d value. Moreover, the mGluR2/3 antagonist MGS0039 (1.0 mg/kg, intraperitoneally) decreased the immobility time of isolation-reared mice in the forced swim test. These results suggest that isolation rearing causes an increase in mGluR2/3 densities in the prefrontal cortex and hippocampus and that the increased receptor function may contribute to pathogenic mechanisms for depression-like behavior of the isolation-reared mice. (C) 2010 Elsevier Ltd. All rights reserved.