The cerebral content of excitatory and inhibitory amino acids in rats following withdrawal of antiepileptic drugs.

V Voiculescu, D Haţegan, E Manole, A Ulmeanu, D Georgescu
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Abstract

The aim of the present study was to investigate the role of amino acids in the increased seizure susceptibility induced by withdrawal of antiepileptic drugs (AEDs). Fifty white Wistar rats treated with AEDs and 30 controls were used. The animals were previously exposed to the acoustic stimulus and only the non responsive were used. The administered AEDs were morphosuximide, ethosuximide, phenobarbital, valproate and gluthetimide. The treatment was discontinued after 2 weeks. The acoustic stimulation was repeated after 2-4 days of abstention. The animals were sacrificed and the amino acids glutamate, aspartate, GABA, glycine and serine were determined in the cortex and the brain stem. The withdrawal of AEDs induced seizure susceptibility in 71% of the rats treated with phenobarbital and in 76% of those receiving morphosuximide. A significant increase of glutamate levels was found in the brain stem following withdrawal of both morphosuximide and ethosuximide. The level of GABA was elevated in the brain stem after valproate and morphosuximide withdrawal. The increase of glutamate concentration can be correlated with the increased seizure susceptibility. The unexpected rise of the GABA level could be interpreted as a compensatory inhibitory mechanism.

停用抗癫痫药物后大鼠大脑兴奋性和抑制性氨基酸的含量。
本研究的目的是探讨氨基酸在抗癫痫药物(AEDs)停药后癫痫易感性增加中的作用。采用aed治疗的Wistar大鼠50只,对照组30只。这些动物之前被暴露在声音刺激下,只有无反应的动物被使用。给药的抗癫痫药有吗啡磺酰亚胺、乙磺酰亚胺、苯巴比妥、丙戊酸酯和谷胱甘肽。2周后停止治疗。停药2 ~ 4天后再次进行声刺激。处死动物,测定皮层和脑干中谷氨酸、天冬氨酸、GABA、甘氨酸和丝氨酸的含量。使用苯巴比妥治疗的大鼠中,71%的大鼠和使用吗啡磺酰亚胺治疗的大鼠中,76%的大鼠停药导致癫痫发作易感性。脑干谷氨酸水平的显著增加是在吗啡和乙氧亚胺停药后发现的。停药后脑干GABA水平升高。谷氨酸浓度升高与癫痫易感性升高相关。GABA水平的意外升高可解释为代偿性抑制机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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