Audiogenic seizure susceptibility is induced by termination of continuous infusion of gamma-aminobutyric acid or an N-methyl-D-aspartic acid Antagonist into the inferior colliculus.
Audiogenic seizure susceptibility is induced by termination of continuous infusion of gamma-aminobutyric acid or an N-methyl-D-aspartic acid Antagonist into the inferior colliculus.
复制标题
听源性癫痫易感性是通过停止向下丘连续输注γ-氨基丁酸或N-甲基-D-天冬氨酸拮抗剂而诱发的。
DOI：
10.1006/exnr.2001.7733
复制
发表时间：
2001
影响因子：
5.3
通讯作者：
Faingold,CL
中科院分区：
文献类型：
--
作者：
Yang,L;Long,C;Faingold,CL
下丘（IC）与遗传形式的听源性癫痫发作（AGS）和乙醇戒断（ETX）期间观察到的AGS中的癫痫发作起始密切相关。已知乙醇可阻断兴奋性氨基酸（EAA）的作用，并增强γ-氨基丁酸（GABA）在几个脑区（包括IC）的作用。本研究探讨了连续阻断N-甲基-d -天冬氨酸（NMDA）受体或连续激活IC中的GABA受体对AGS敏感性的影响。这涉及使用Alzet渗透微型泵以0.25 μl/h输注GABA（1 M）或竞争性NMDA拮抗剂dl-2-氨基-7-膦酰基庚酸（AP 7，1 mM）7天。突然终止输液后，AGS的敏感性开始在30分钟。AGS的发病率分别为38.9%和56.3%以下GABA和AP 7撤出，分别。在戒断过程中观察到的AGS行为，包括疯狂奔跑和弹跳阵挛，与ETX过程中由声学刺激引起的行为非常相似。AGS敏感性持续数小时，13%的动物持续长达6个月。目前的研究结果支持减少GABA能和升高的谷氨酸能功能的IC作为AGS启动的关键机制和网站。本研究，再加上以前的证据表明，慢性乙醇暴露减少GABA介导的抑制和增强EAA介导的兴奋，表明这些氨基酸受体介导的IC的改变是在乙醇戒断过程中启动AGS的关键因素。
The inferior colliculus (IC) is strongly implicated in seizure initiation in a genetic form of audiogenic seizures (AGS) and in AGS observed during ethanol withdrawal (ETX). Ethanol is known to block the actions of excitatory amino acids (EAA) and enhance the actions of γ-aminobutyric acid (GABA) in several brain areas, including the IC. The present study investigated the effects on susceptibility to AGS following withdrawal from continuous blockade of N-methyl-d -aspartic acid (NMDA) receptors or continuous activation of GABA receptors in the IC. This involved infusion of GABA (1 M) or a competitive NMDA antagonist, dl -2-amino-7-phosphonoheptanoic acid (AP7, 1 mM), at 0.25 μl/h for 7 days using an Alzet osmotic minipump. Following abrupt termination of the infusion, AGS susceptibility began at 30 min. The incidence of AGS was 38.9 and 56.3% following GABA and AP7 withdrawal, respectively. The AGS behaviors observed during withdrawal, which included wild running and bouncing clonus, were very similar to those evoked by acoustic stimuli during ETX. AGS susceptibility lasted for several hours and in 13% of animals persisted for up to 6 months. The current results support diminished GABAergic and elevated glutamatergic function in the IC as the critical mechanisms and sites for AGS initiation. The present study, coupled with previous evidence that chronic ethanol exposure reduced GABA-mediated inhibition and enhanced EAA-mediated excitation, suggests that these amino acid receptor-mediated alterations in the IC are key elements in initiating AGS during ethanol withdrawal.