Decreased GABA effectiveness in the inferior colliculus neurons during ethanol withdrawal in rats susceptible to audiogenic seizures.
Decreased GABA effectiveness in the inferior colliculus neurons during ethanol withdrawal in rats susceptible to audiogenic seizures.
复制标题
在易发生听源性癫痫发作的大鼠乙醇戒断期间，下丘神经元的 GABA 有效性降低。
DOI：
10.1016/0006-8993(96)00304-6
复制
发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Faingold,CL
中科院分区：
文献类型：
--
作者：
N'Gouemo,P;Caspary,DM;Faingold,CL
下丘(IC)是乙醇戒断(ETX)大鼠听源性惊厥(AGS)神经元网络的起始部位。相当多的证据支持伽玛-氨基丁酸(GABA)介导的抑制在IC的正常声处理中的作用。改变的GABA介导的IC抑制被认为是控制AGS启动的重要因素。本研究采用微离子导入法检测了GABA对声诱发中枢核(ICC)神经元反应的影响。比较了正常对照组和表现出高听源性惊厥敏感性(100%AGS)(HAG)的一组动物和低(平均33%)AGS发生率(LAGS)的一组动物的GABA效果。每日三次注射乙醇(9-15g/kg/天)，连续4天，足以维持中等程度的中毒。在HAGS动物中观察到强直-阵挛发作，而LAGS大鼠表现出不那么严重的癫痫发作，主要包括狂奔。在对照组和接受ETX的动物中，GABA的离子导入持续抑制WE神经元的放电。然而，在HAGS组，产生50%ICC神经元放电减少所需的GABA平均剂量(电流)几乎是对照组的两倍。在LAGS组中，GABA抑制50%的平均剂量约为对照组的一半。这两个差异在统计学上都是显著的。这些数据表明，易感HAG动物的IC神经元中GABA有效性的降低是导致ETX期间出现的严重AGS在这些动物中传播的重要机制。
The inferior colliculus (IC) is the initiation site in the neuronal network for audiogenic seizure (AGS) in rats undergoing ethanol withdrawal (ETX). Considerable evidence supports a role of gamma-aminobutyric acid (GABA)-mediated inhibition in normal acoustic processing in the IC. Altered GABA-mediated inhibition in the IC is suggested to be important in the control of AGS initiation. The present study used microiontophoresis to examine the effectiveness of GABA on acoustically-evoked neuronal responses in the central nucleus of the IC (ICc). GABA effectiveness was compared in normal controls and a group of animals displaying high audiogenic seizure susceptibility (100% AGS) (HAGS), and a group exhibiting a low (mean, 33%) incidence of AGS (LAGS). Ethanol was administered for 4 days in three daily doses (9–15 g/kg/day) sufficient to maintain a moderate degree of intoxication. Tonic-clonic seizures were observed in HAGS animals, while LAGS rats exhibited less severe seizures, consisting primarily of wild running. Iontophoretic application of GABA consistently inhibited We neuronal firing in controls and in animals undergoing ETX. However, the mean dose (current) of GABA required to produce a 50% reduction of the ICc neuronal firing in the HAGS group was nearly twice that of the control animals. The mean dose of GABA for 50% inhibition in the LAGS group was about one-half that of the control group. Both of these differences were statistically significant. These data suggest that decreased GABA effectiveness in the IC neurons of HAGS susceptible animals is an important mechanism contributing to the propagation of severe AGS seen during ETX in these animals.