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体外下丘脑中的细胞内反应异常与乙醇戒断性癫痫易感性相关。

Inferior colliculus intracellular response abnormalities in vitro associated with susceptibility to ethanol withdrawal seizures.

作者信息

Evans M S, Li Y, Faingold C

机构信息

Department of Neurology, Southern Illinois University School of Medicine, Springfield, USA.

出版信息

Alcohol Clin Exp Res. 2000 Aug;24(8):1180-6.

PMID:10968655
Abstract

During ethanol withdrawal (ETX), rats become susceptible to audiogenic seizures in which the inferior colliculus (IC) is known to play a critical role. The present study examined changes in membrane properties that occurred in IC dorsal cortex (ICd) neurons in brain slices from rats after 4 days of three times daily intragastric ethanol, which is proposed to be an analog of binge drinking. Compared with neurons from control animals, ICd neurons during ETX had action potentials (APs) with lower thresholds, a greater incidence of spontaneous APs, a reduced degree of spike firing adaptation, and an increased incidence of anode-break firing. With synaptic stimulation, epileptiform firing was seen in nearly 50% of ICd neurons during ETX but never was seen in normal ICd neurons except after perfusion of the gamma-aminobutyric acid type A (GABA(A)) antagonist bicuculline. Paired pulse responses of ICd neurons were also abnormal during ETX. Thus, in 75% of normal rats, paired synaptic stimuli inhibited the second response, but during ETX all neurons tested showed paired pulse facilitation. These aberrant membrane and synaptic properties provide direct evidence for the hyperexcitability of IC neurons during ETX. They may be due, in part, to changes in GABAergic and glutamatergic neurotransmission known to be produced during withdrawal after continued ethanol administration.

摘要

在乙醇戒断(ETX)期间,大鼠会变得易患听源性癫痫发作,已知下丘(IC)在其中起关键作用。本研究检测了每日三次灌胃给予乙醇4天的大鼠脑片中IC背侧皮质(ICd)神经元的膜特性变化,这种给药方式被认为是暴饮的一种模拟。与对照动物的神经元相比,ETX期间的ICd神经元动作电位(APs)阈值更低,自发APs发生率更高,动作电位发放适应性程度降低,阳极断裂发放发生率增加。通过突触刺激,ETX期间近50%的ICd神经元出现癫痫样发放,但正常ICd神经元中除了灌注γ-氨基丁酸A型(GABA(A))拮抗剂荷包牡丹碱后从未出现过。ETX期间ICd神经元的双脉冲反应也异常。因此,在75%的正常大鼠中,双突触刺激会抑制第二个反应,但在ETX期间,所有测试的神经元都表现出双脉冲易化。这些异常的膜和突触特性为ETX期间IC神经元的过度兴奋性提供了直接证据。它们可能部分归因于持续给予乙醇后戒断期间已知产生的GABA能和谷氨酸能神经传递的变化。

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