Anxiolytic-like activity of the mGluR5 antagonist MPEP - A comparison with diazepam and buspirone
Anxiolytic-like activity of the mGluR5 antagonist MPEP - A comparison with diazepam and buspirone
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DOI：
10.1016/s0091-3057(02)00828-6
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发表时间：
2002-09-01
影响因子：
3.6
通讯作者：
Varney, MA
中科院分区：
文献类型：
--
作者：
Brodkin, J;Busse, C;Varney, MA
代谢型谷氨酸受体亚型5（mGluR 5）的选择性和全身活性拮抗剂2-甲基-6-（苯乙炔基）吡啶（MPEP）在啮齿类动物的应激和焦虑（高架十字迷宫、电击探针掩埋、大理石掩埋、社会互动和应激诱导的高热）的许多非条件试验中显示出抗焦虑样活性。在这份报告中，我们扩展这些观察发现使用无条件模型的焦虑，包括三个模型的条件焦虑，比较活动的MPEP临床使用的抗焦虑药，地西泮，丁螺环酮。MPEP和地西泮，但不是丁螺环酮，表现出抗焦虑样活性的恐惧增强惊吓（FPS）模型。在条件超声发声（USV）程序中，NIPEP、地西泮和丁螺环酮将发声减少到相似的程度。在改良的Geller-Seifter程序中，MPEP、地西泮和丁螺环酮显示出统计学显著的抗焦虑样活性，增加了惩罚反应的数量。因此，这些发现证实并扩展了先前的报道，即MPEP在大鼠中表现出抗焦虑样活性，并表明mGluR 5拮抗剂的开发可能提供治疗焦虑症的新方法。(C)2002年爱思唯尔科技有限公司All rights reserved.
The selective and systemically active antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)pyridine (MPEP) was shown to display anxiolytic-like activity in a number of unconditioned assays of stress and anxiety (elevated plus maze, shock probe burying, marble burying, social interaction, and stress-induced hyperthermia) in rodents. In this report, we extend these observations found using unconditioned models of anxiety to include three models of conditioned anxiety, comparing the activity of MPEP to the clinically used anxiolytics, diazepam, and buspirone. MPEP and diazepam, but not buspirone, showed anxiolytic-like activity in the fear-potentiated startle (FPS) model. In a conditioned ultrasonic vocalization (USV) procedure, NIPEP, diazepam, and buspirone reduced vocalizations to a similar degree. In the modified Geller-Seifter procedure, MPEP, diazepam, and buspirone displayed statistically significant anxiolytic-like activity, increasing the number of punished responses. Thus, these findings confirm and extend previous reports that MPEP exhibits anxiolytic-like activity in rats, and suggests that development of mGluR5 antagonists may provide a novel approach to treating anxiety disorders. (C) 2002 Elsevier Science Inc. All rights reserved.