-methyl-D-aspartic acid receptors (NMDARs) are the most studied receptors in mammalian brains. Their role in depression, cognition, schizophrenia, learning and memorization, Alzheimer's disease, and more is well documented. In the search for new drug candidates in depression, intensive studies have been conducted. Compounds that act by influencing NMDARs have been particularly intensively investigated following the success of ketamine in clinics. Unfortunately, the side effects associated with ketamine do not allow it to be useful in all cases. Therefore, it is important to learn about new unknown mechanisms related to NMDAR activation and study the impact of changes in the excitatory synapse environment on this receptor. Both direct and intermediary influence on NMDARs via mGluRs and COX-2 are effective. Our prior studies showed that both mGluRs ligands and COX-2 inhibitors are potent in depression-like and cognitive studies through mutual interactions. The side effects associated with imipramine administration, e.g., memory impairment, were improved when inhibiting COX-2. Therefore, this study is a trial that involves searching for modifications in NMDARs in mouse brains after prolonged treatment with MTEP (mGluR5 antagonist), NS398 (COX-2 inhibitor), or imipramine (tricyclic antidepressant). The prefrontal cortex (PFC) and hippocampus (HC) were selected for PCR and Western blot analyses. Altered expression of or genes after treatment was found. The observed effects were more potent when COX-2 was inhibited. The finding described here may be vital when searching for new drugs acting via NMDARs without the side effects related to cognition.

中文翻译：

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环加氧酶 2 抑制通过与小鼠大脑中的 mGluR5 相互作用影响 GluN2A/GluN2B 受体亚基的比例

-甲基-D-天冬氨酸受体（NMDAR）是哺乳动物大脑中研究最多的受体。它们在抑郁症、认知、精神分裂症、学习和记忆、阿尔茨海默病等方面的作用已有充分记录。在寻找治疗抑郁症的新候选药物方面，已经进行了深入的研究。随着氯胺酮在临床上的成功，通过影响 NMDAR 发挥作用的化合物得到了特别深入的研究。不幸的是，与氯胺酮相关的副作用使其无法在所有情况下发挥作用。因此，了解与 NMDAR 激活相关的新的未知机制并研究兴奋性突触环境的变化对该受体的影响非常重要。通过 mGluR 和 COX-2 对 NMDAR 的直接和中间影响都是有效的。我们之前的研究表明，mGluRs 配体和 COX-2 抑制剂通过相互相互作用在抑郁症和认知研究中发挥作用。当抑制COX-2时，与丙咪嗪给药相关的副作用，例如记忆障碍，得到改善。因此，本研究是一项涉及寻找长期接受 MTEP（mGluR5 拮抗剂）、NS398（COX-2 抑制剂）或丙咪嗪（三环抗抑郁药）治疗后小鼠大脑中 NMDAR 修饰的试验。选择前额皮质 (PFC) 和海马 (HC) 进行 PCR 和蛋白质印迹分析。发现治疗后基因表达发生改变。当 COX-2 受到抑制时，观察到的效果更有效。当寻找通过 NMDAR 起作用且不产生与认知相关的副作用的新药物时，此处描述的发现可能至关重要。