Morimoto K, Holmes K H, Goddard G V
Exp Neurol. 1987 Jul;97(1):17-34. doi: 10.1016/0014-4886(87)90279-2.
In our previous studies, we hypothesized that activation and subsequent collapse of GABA-mediated inhibition during tetanus is an important seizure-triggering mechanism in the kindled epileptogenic focus. To examine this hypothesis, in the present study, we investigated the effects of pharmacological manipulations of the kindled amygdala with several drugs, and measured the kindled seizures as well as the EEG events during tetanus. The results obtained were: (i) The selective GABA-A agonist, muscimol (1 and 5 nM/1 microliter), suppressed kindled seizures in a dose-dependent fashion, and the 5 nM muscimol significantly prolonged EEG suppression and reduced the number of oscillations in the subsequent rhythmic synchronous discharge. Similar effects followed systemic injection of diazepam (2 mg/kg). (ii) The selective GABA-B agonist, baclofen (5 nM), had no effect on kindled seizures nor on the EEG events during tetanus. (iii) The NMDA antagonist, 2-amino-5-phosphonovaleric acid (80 nM), significantly reduced the afterdischarge duration and significantly delayed the appearance of the rhythmic synchronous discharge. However, these effects were not observed immediately, but 24 to 72 h after microinjection. (iv) The muscarinic cholinergic antagonist, atropine (40 and 80 nM), suppressed kindled seizures in a dose-dependent fashion, but the atropine caused marked synchronous discharge both in the awake resting EEG and during tetanic stimulation. We conclude that the GABA-A system, including the benzodiazepine system, is more involved in the seizure-triggering mechanism of amygdala kindling than the GABA-B system, that there is an interaction between the GABA-A and NMDA system, and that the cholinergic participation is independent of the primary seizure-triggering mechanisms.
在我们之前的研究中，我们假设破伤风期间GABA介导的抑制作用的激活及随后的崩溃是点燃癫痫灶中一种重要的癫痫发作触发机制。为检验这一假设，在本研究中，我们用几种药物研究了对点燃杏仁核进行药理学操作的效果，并测量了点燃性癫痫发作以及破伤风期间的脑电图事件。得到的结果如下：(i) 选择性GABA-A激动剂蝇蕈醇（1和5 nM/1微升）以剂量依赖方式抑制点燃性癫痫发作，5 nM蝇蕈醇显著延长脑电图抑制时间并减少随后节律性同步放电中的振荡次数。全身注射地西泮（2 mg/kg）也有类似效果。(ii) 选择性GABA-B激动剂巴氯芬（5 nM）对点燃性癫痫发作及破伤风期间的脑电图事件均无影响。(iii) NMDA拮抗剂2-氨基-5-磷酰基戊酸（80 nM）显著缩短放电后持续时间并显著延迟节律性同步放电的出现。然而，这些作用不是在微量注射后立即观察到的，而是在24至72小时后出现。(iv) 毒蕈碱胆碱能拮抗剂阿托品（40和80 nM）以剂量依赖方式抑制点燃性癫痫发作，但阿托品在清醒静息脑电图及强直刺激期间均引起明显的同步放电。我们得出结论，包括苯二氮䓬系统在内的GABA-A系统比GABA-B系统更参与杏仁核点燃的癫痫发作触发机制，GABA-A和NMDA系统之间存在相互作用，且胆碱能参与独立于主要的癫痫发作触发机制。
