N'Gouemo P, Caspary D M, Faingold C L
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-1222, USA.
Brain Res. 1996 Jun 17;724(2):200-4. doi: 10.1016/0006-8993(96)00304-6.
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 ICc 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.
下丘（IC）是经历乙醇戒断（ETX）的大鼠听源性癫痫（AGS）神经网络中的起始部位。大量证据支持γ-氨基丁酸（GABA）介导的抑制在IC正常听觉处理中的作用。IC中GABA介导的抑制改变被认为在AGS起始控制中很重要。本研究使用微离子电泳来检查GABA对IC中央核（ICc）中听觉诱发神经元反应的有效性。在正常对照组以及一组表现出高听源性癫痫易感性（100% AGS）（HAGS）的动物和一组AGS发生率低（平均33%）（LAGS）的动物中比较了GABA的有效性。乙醇以每日三次剂量（9 - 15 g/kg/天）给药4天，足以维持中度中毒程度。在HAGS动物中观察到强直阵挛性癫痫发作，而LAGS大鼠表现出不太严重的癫痫发作，主要包括狂奔。GABA的离子电泳应用在对照组和经历ETX的动物中均持续抑制ICc神经元放电。然而，在HAGS组中使ICc神经元放电减少50%所需的GABA平均剂量（电流）几乎是对照动物的两倍。LAGS组中50%抑制所需的GABA平均剂量约为对照组的一半。这两个差异均具有统计学意义。这些数据表明，HAGS易感动物IC神经元中GABA有效性降低是导致这些动物在ETX期间出现严重AGS传播的重要机制。
