Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum
Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum
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DOI：
10.1016/j.neuropharm.2007.01.008
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发表时间：
2007-04-01
影响因子：
4.7
通讯作者：
Avoli, M.
中科院分区：
文献类型：
--
作者：
D'Antuono, M.;Kawasaki, H.;Avoli, M.
在体外切片制备领域和细胞内的记录，以确定是否抗癫痫药物托吡酯和拉莫三嗪调节胆碱能兴奋大鼠下托。卡巴胆碱（CCh，70-100 μ M）浴应用诱导：（i）自发和同步场振荡（持续时间=高达7秒），反映了细胞内去极化与节律性动作电位爆发;和（ii）去极化平台。与响应短暂（50-100 ms）细胞内去极化电流脉冲的动作电位放电相关的电位（DPP，持续时间=最多2.5 s）。离子型β-amatergic受体拮抗剂取消了不影响DPP的场振荡，而阿托品（1 μ M）显着降低这两种类型的活动。托吡酯（10-100 μ M，它= 8-13片）或拉莫三嗪（50-400 μ M，n = 3-12）以剂量依赖性方式减少，并最终消除，CCh诱导的场振荡。在托吡酯应用期间，这些作用伴随着DPP显著降低。当这些抗癫痫药物在存在CCh +离子型谷氨酸能和GABA受体拮抗剂的情况下对DPP进行测试时，只有托吡酯降低DPP（n = 5-19/剂量; IC 50 - 18 μ M，n = 48）。托吡酯在代谢型谷氨酸受体拮抗剂（n = 5）中诱导了类似的作用，但不影响DPP。因此，托吡酯和拉莫三嗪减少大鼠海马下托中的胆碱诱导的癫痫样同步，但只有托吡酯是有效的控制DPP。我们建议，毒蕈碱受体介导的兴奋代表了一些抗癫痫药物，如托吡酯的作用的目标。(c)2007爱思唯尔有限公司保留所有权利。
Field and intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drugs topiramate and lamotrigine modulate cholinergic excitation in the rat subiculum. Bath application of carbachol (CCh, 70-100 mu M) induced: (i) spontaneous and synchronous field oscillations (duration = up to 7 s) that were mirrored by intracellular depolarizations with rhythmic action potential bursts; and (ii) depolarizing plateau. potentials (DPPs, duration = up to 2.5 s) associated with action potential discharge in response to brief (50-100 ms) intracellular depolarizing current pulses. Ionotropic glutamatergic receptor antagonists abolished the field oscillations without influencing DPPs, while atropine (1 mu M) markedly reduced both types of activity. Topiramate (10-100 mu M, it = 8-13 slices) or lamotrigine (50-400 mu M, n = 3-12) decreased in a dose-dependent manner, and eventually abolished, CCh-induced field oscillations. During topiramate application, these effects were accompanied by marked DPP reduction. When these antiepileptic drugs were tested on DPPs recorded in the presence of CCh + ionotropic glutamatergic and GABA receptor antagonists, only topiramate reduced DPPs (n = 5-19/dose; IC50 - 18 mu M, n = 48). Similar effects were induced by topiramate during metabotropic glutamate receptor antagonism (n = 5), which did not influence DPPs. Thus, topiramate and lamotrigine reduce CCh-induced epileptiform synchronization in the rat subiculum but only topiramate is effective in controlling DPPs. We propose that muscarinic receptor-mediated excitation represents a target for the action of some antiepileptic drugs such as topiramate. (c) 2007 Elsevier Ltd. All rights reserved.