Decreased GABA and increased glutamate receptor-mediated activity on inferior colliculus neurons in vitro are associated with susceptibility to ethanol withdrawal seizures
Decreased GABA and increased glutamate receptor-mediated activity on inferior colliculus neurons in vitro are associated with susceptibility to ethanol withdrawal seizures
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DOI：
10.1016/s0006-8993(00)02342-8
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发表时间：
2000-06-23
期刊：
影响因子：
2.9
通讯作者：
Evans, MS
中科院分区：
文献类型：
--
作者：
Faingold, C;Li, Y;Evans, MS
在乙醇依赖性大鼠中停止乙醇给药导致乙醇戒断（ETX）综合征，包括听源性癫痫发作（AGS）。下丘（IC）是AGS的起始部位，IC神经元的膜特性在ETX期间表现出过度兴奋。先前的研究观察到，ETX改变了某些大脑部位的GABA和谷氨酸神经传递。本研究评价了乙醇灌胃给药大鼠脑片IC背侧皮层（ICd）神经元内毒素（ETX）过程中GABA或谷氨酸拮抗剂的突触特性和作用，每日3次，连续4天。在ETX期间观察到自发动作电位（AP）显著增加。内毒素刺激可使下丘连合兴奋性突触后电位（EPSP）的宽度、面积和上升时间显著增加。快EPSP对非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2，3-二酮（CNQX）的阻断敏感，慢EPSP对NMDA受体拮抗剂2-氨基-5-膦酰基戊酸（AP 5）的阻断敏感。然而，在ETX期间，阻断这些EPSP所需的CNQX或AP 5的浓度显著升高。GABA（A）拮抗剂荷包牡丹碱（bicuculline）可阻断正常和内毒素大鼠ICd神经元的抑制性突触后电位（IPSPs）。然而，在ETX期间IPSP显示出对荷包牡丹碱的显著更高的敏感性。这些数据表明，IC中GABA（A）介导的抑制降低和谷氨酸介导的兴奋性增加可能都是ETX期间ACS起始的关键机制，这与遗传形式的AGS中的观察结果相似。这些AGS形式中IC神经传递的共同变化可能是使AGS和其他形式的听觉系统病理生理学受益的一般机制，其中涉及IC。(C)2000 Elsevier Science B. V.保留所有权利。
Cessation of ethanol administration in ethanol-dependent rats results in an ethanol withdrawal (ETX) syndrome, including audiogenic seizures (AGS). The inferior colliculus (IC) is the initiation site fur AGS, and membrane properties of IC neurons exhibit hyperexcitability during ETX. Previous studies observed that ETX alters GABA and glutamate neurotransmission in certain brain sites. The present study evaluated synaptic properties and actions of GABA or glutamate antagonists during ETX in IC dorsal cortex (ICd) neurons in brain slices from rats treated with ethanol intragastrically 3 times daily for 4 days. A significant increase of spontaneous action potentials (APs) was observed during ETX. The width, area and rise time of excitatory postsynaptic potentials (EPSPs) evoked by stimulation in the commissure of IC were significantly elevated during ETX. A fast EPSP was sensitive to block by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and a slow EPSP was sensitive to the NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5). However, during ETX the concentration of CNQX or AP5 needed to block these EPSPs was elevated significantly. Inhibitory postsynaptic potentials (IPSPs) in ICd neurons evoked in both normal and ETX rats were blocked by the GABA(A) antagonist, bicuculline. However, IPSPs during ETX displayed a significantly greater sensitivity to bicuculline. These data indicate that decreased GABA(A)-mediated inhibition and increased glutamate-mediated excitability in IC may both be critical mechanisms of ACS initiation during ETX, which is similar to observations in a genetic form of AGS. The common changes in IC neurotransmission in these AGS forms may be general mechanisms subserving AGS and other forms of auditory system pathophysiology in which the IC is implicated. (C) 2000 Elsevier Science B.V. All rights reserved.