Kang M, Spigelman I, Sapp D W, Olsen R W
Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, CA 90024-1735, USA.
Brain Res. 1996 Feb 19;709(2):221-8. doi: 10.1016/0006-8993(95)01274-5.
GABA(A) receptor-mediated function was studied in rats treated with chronic intermittent ethanol (CIE). Rats were given 60 doses of 6g/kg ethanol every 24 h by gastric intubation, with repeated intoxicating and withdrawal episodes leading to a kindling-like increase in seizure susceptibility (Kokka et al., Alcohol: Clin. Exp. Res., 17 (1993) 525-531). Efflux of 36Cl-, evoked by application of muscimol, a measure of GABA(A) receptor function, was examined in 300 mu m slices obtained from frontal, parietal, and temporal cortex, hippocampus, and inferior colliculus, one day after the last administration of ethanol. Compared to controls, the 36Cl- efflux in hippocampal slices of CIE rats was significantly reduced by 29%, while there were no changes in the other brain regions studied. In hippocampal slices, paired-pulse inhibition in CA1 pyramidal neurons, measured extracellularly using homosynaptic orthodromic stimulation at an interval of 10 ms, was significantly reduced in CIE rats. A significant decrease by 40% both at 2 and 40 days after 60 doses of ethanol was found, implying a persistent decrease in GABA(A) receptor-mediated inhibition in CIE rats. These reductions in paired-pulse inhibition are consistent with the decrease in the pentylenetetrazol (PTZ) seizure threshold which was previously observed in CIE rats. Therefore, we suggest that this reduction of GABA(A) receptor-mediated inhibition contributes to the persistent increase in seizure susceptibility of CIE rats.
研究了慢性间歇性乙醇（CIE）处理的大鼠中GABA(A)受体介导的功能。通过胃内插管，每24小时给大鼠给予60次剂量为6g/kg的乙醇，反复的中毒和戒断发作导致癫痫易感性出现类似点燃效应的增加（Kokka等人，《酒精：临床与实验研究》，17 (1993) 525 - 531）。在最后一次给予乙醇一天后，从额叶、顶叶、颞叶皮质、海马体和下丘获得的300μm切片中，检测了由蝇蕈醇应用诱发的36Cl-外流，这是GABA(A)受体功能的一种测量方法。与对照组相比，CIE大鼠海马切片中的36Cl-外流显著减少了29%，而在所研究的其他脑区没有变化。在海马切片中，使用间隔10ms的同突触正向刺激细胞外测量CA1锥体神经元的配对脉冲抑制，CIE大鼠的该抑制显著降低。在给予60次乙醇剂量后的第2天和第40天均发现显著降低40%，这意味着CIE大鼠中GABA(A)受体介导的抑制持续降低。这些配对脉冲抑制的降低与先前在CIE大鼠中观察到的戊四氮（PTZ）癫痫阈值降低一致。因此，我们认为GABA(A)受体介导的抑制的这种降低导致了CIE大鼠癫痫易感性的持续增加。
