Activation of group 2 metabotropic glutamate receptors reduces behavioral and electrographic correlates of pilocarpine induced status epilepticus.
Activation of group 2 metabotropic glutamate receptors reduces behavioral and electrographic correlates of pilocarpine induced status epilepticus.
复制标题
DOI：
10.1016/j.eplepsyres.2013.10.009
复制
发表时间：
2014-02
影响因子：
2.2
通讯作者：
Godwin DW
中科院分区：
文献类型：
--
作者：
Caulder EH;Riegle MA;Godwin DW
癫痫的新疗法是必要的，因为许多癫痫患者对药物有抵抗力。代谢型谷氨酸受体(MGluRs)，特别是mGluR2和mGluR2，由于其在控制突触释放中的作用，可能成为抗癫痫的靶点。在这项研究中，我们使用了第二组mGluR激动剂LY379268，两种mGluR2特异性正变构调节剂之一BINA或CBiPES，或者BINA和LY379268的鸡尾酒，在使用SE的匹罗卡品模型的一系列实验中。在一项研究中，小组在匹罗卡品之前15分钟接受治疗，而在第二项研究中，小组在SE开始后接受治疗，以确定这些药物是否可以减缓SE的发展和进展。我们测量了5期癫痫发作次数、首次发作的潜伏期和最大racine评分来表征癫痫发作的严重程度。我们使用功率分析对植入电极的小鼠脑电进行了分析。我们发现，LY379268治疗前后在与癫痫相关的EEG带宽中均有效地降低了行为相关系数和功率，而CBiPES的效果较差，BINA无效。这些数据总体上支持mGluR2继续开发新的抗癫痫药物的药理作用，尽管进一步研究其他药物和浓度将是必要的。
Novel treatments for epilepsy are necessary because many epilepsy patients are resistant to medication. Metabotropic glutamate receptors (mGluRs), specifically mGluR 2 and 3, may serve as antiepileptic targets because of their role in controlling synaptic release. In this study, we administered a Group 2 mGluR agonist, LY379268, one of two mGluR2-specific positive allosteric modulators, BINA or CBiPES, or a cocktail of both BINA and LY379268 in a series of experiments using the pilocarpine model of SE. In one study, groups received treatments 15 minutes prior to pilocarpine, while in a second study groups received treatments after SE had been initiated to determine whether the drugs could reduce development and progression of SE. We measured bouts of stage 5 seizures, latency to the first seizure, and the maximum Racine score to characterize the seizure severity. We analyzed mouse EEG with implanted electrodes using a power analysis. We found that pretreatment and posttreatment with LY379268 was effective at reducing both behavioral correlates and power in EEG bandwidths associated with seizure, while CBiPES was less effective and BINA was ineffective. These data generally support continued development of mGluR2 pharmacology for novel antiepileptic drugs, though further study with additional drugs and concentrations will be necessary.