Anxiolytic-like effects of mGlu 1 and mGlu5 receptor antagonists in rats
Anxiolytic-like effects of mGlu 1 and mGlu5 receptor antagonists in rats
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DOI：
10.1016/j.ejphar.2005.03.028
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发表时间：
2005-05-02
影响因子：
5
通讯作者：
Danysz, W
中科院分区：
文献类型：
--
作者：
Pietraszek, M;Sukhanov, I;Danysz, W
本研究的目的是比较代谢型谷氨酸受体1（mGlu）拮抗剂EMQMCM（（3-乙基-2-甲基-喹啉-6-基）-（4-甲氧基-环己基）-甲酮甲磺酸盐）和mGlu 5受体拮抗剂MTEP（[（2-甲基-1，3-噻唑-4-基）乙炔基]吡啶）和MPEP（2-甲基-6-（苯乙炔基）吡啶）在焦虑动物模型中的抗焦虑活性。在高架十字迷宫中，地西泮（1 mg/kg）而不是mGlu 1或mGlu 5受体拮抗剂诱导了抗焦虑样作用。同时，MTEP（2.5和5 mg/kg）、EMQMCM（5 mg/kg）和地西泮（2 mg/kg）均显著抑制恐惧增强惊吓。在情境恐惧条件化实验中，MTEP（1.25和2.5，但不是5 mg/kg）和EMQMCM（0.6至5 mg/kg）减弱了冻结反应。在Geller-Seifter冲突实验中，MPEP（1和3 mg/kg）、MTEP（3 mg/kg）、利氮卓（10和20 mg/kg）和咪达唑仑（1 mg/kg）均能促进惩罚反应，而ECMQCM在3 mg/kg剂量下无明显作用。总之，本数据进一步支持I组mGlu受体拮抗剂的显著抗焦虑潜力，同时表明mGlu 1受体拮抗剂的作用可能取决于实验程序，并且可能与mGlu 5受体拮抗剂的作用在性质上不同。(c)2005 Elsevier B. V.保留所有权利。
The purpose of the present study was to compare anxiolytic activity of the metabotropic glutamate receptor 1 (mGlu) antagonist, EMQMCM ((3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and the mGlu5 receptor antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine) and MPEP (2-methyl-6-(phenylethynyl)pyridine) in animal models of anxiety. In the elevated plus maze, diazepam (1 mg/kg), but not the mGlu1 or mGlu5 receptor antagonists induced anxiolytic-like effects. Meanwhile, MTEP (2.5 and 5 mg/kg), EMQMCM (5 mg/kg), and diazepam (2 mg/kg) all significantly inhibited fear potentiated startle. In the contextual fear conditioning test, MTEP (1.25 and 2.5 but not 5 mg/kg) and EMQMCM (0.6 to 5 mg/kg) attenuated freezing responding. In the Geller-Seifter conflict test, MPEP (1 and 3 mg/kg), MTEP (3 mg/kg), chlordiazepoxide (10 and 20 mg/kg) and midazolam (1 mg/kg) all facilitated punished responding, while ECMQCM failed to produce any significant effects up to 3 mg/kg dose. To summarise, the present data further support a significant anxiolytic potential of group I mGlu receptor antagonists, while suggesting the effects of mGlu1 receptor antagonists may depend on the experimental procedure and may be qualitatively different from those of mGlu5 receptor antagonists. (c) 2005 Elsevier B.V. All rights reserved.