Smolders I, Van Belle K, Ebinger G, Michotte Y
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universteit Brussel, Belgium.
Eur J Pharmacol. 1997 Jan 14;319(1):21-9. doi: 10.1016/s0014-2999(96)00830-8.
Limbic seizures were provoked in freely moving rats by intrahippocampal administration of the muscarinic receptor agonist pilocarpine via a microdialysis probe (10 mM for 40 min at 2 microliters/min). Changes in extracellular hippocampal and cerebellar glutamate, aspartate and gamma-aminobutyric acid (GABA) levels were monitored during and after pilocarpine administration. Effects of systemic or local administration of anticonvulsants on the seizures and concomitant changes in amino-acid concentrations, were investigated. Pilocarpine-induced seizures were completely abolished after intraperitoneal premedication for 7 days with phenobarbital (15 mg/kg per day) and after intrahippocampal administration of 10 mM phenobarbital and 1 mM carbamazepine (180 min at 2 microliters/min). Rats premedicated with carbamazepine (5 mg/kg per day) still developed seizures. The changes in extracellular hippocampal amino-acid levels suggest that glutamate, aspartate and GABA are not involved in seizure onset, but may play a role in seizure maintenance and/or spread in the pilocarpine animal model of epilepsy. The increases in extracellular amino acids in ipsi- and contralateral cerebellum following limbic seizures provoked in the hippocampus, probably play a role in the 'reversed' diaschisis phenomenon.
通过微透析探针向自由活动的大鼠海马内注射毒蕈碱受体激动剂毛果芸香碱（10 mM，以2微升/分钟的速度注射40分钟）来诱发边缘叶癫痫发作。在注射毛果芸香碱期间及之后，监测细胞外海马和小脑谷氨酸、天冬氨酸和γ-氨基丁酸（GABA）水平的变化。研究了全身或局部给予抗惊厥药对癫痫发作以及氨基酸浓度伴随变化的影响。在用苯巴比妥（每天15 mg/kg）腹腔预处理7天后，以及在海马内注射10 mM苯巴比妥和1 mM卡马西平（以2微升/分钟的速度注射180分钟）后，毛果芸香碱诱发的癫痫发作完全被消除。用卡马西平（每天5 mg/kg）预处理的大鼠仍会发生癫痫发作。细胞外海马氨基酸水平的变化表明，谷氨酸、天冬氨酸和GABA不参与癫痫发作的起始，但可能在癫痫持续状态和/或在毛果芸香碱癫痫动物模型中的扩散中起作用。海马诱发边缘叶癫痫发作后，同侧和对侧小脑细胞外氨基酸的增加，可能在“逆向”远隔效应现象中起作用。
