Establishment of newly found tremor rat as absence seizure model and pharmacological usefulness

研究建立了新发现的震颤大鼠（tm/tm）的产生和维持，表现出缺席样癫痫发作和这种动物的药理作用。(1)幼龄震颤大鼠在左侧海马CA3区发现脑电图可能出现峰波复合体的病灶，随着年龄增长，峰波复合体向双侧皮层和右侧海马CA3区发展。(2)常规抗癫痫药物对自发性癫痫大鼠（SER）的缺席样癫痫发作的抑制作用与人的相似：乙氧亚胺、甲美二酮、丙戊酸酯和苯巴比妥对癫痫发作有抑制作用，而苯妥英对癫痫发作无抑制作用。(3)海马切片制备过程中，单次刺激CA3锥体细胞的苔藓纤维可诱导长时间的去极化移位伴重复性放电。Ca^<2+>拮抗剂尼卡地平可抑制该反应，提示海马CA3锥体细胞中Ca^<2+>电流增强可能是由于Ca^<2+>通道异常所致。(4)利用急性游离海马细胞获得对尼卡地平敏感的Ca^<2+>电流。这些结果提示震颤大鼠可用于评价抗癫痫药物的急性和慢性作用，以及研究缺席样癫痫发作的机制。

Studies were performed to establish production and maintenance of newly found tremor rat (tm/tm) that showed absence-like seizures and the pharmacological usefulness of this animal.(1) The possible focus that shows spikes and wave complex in EEG was found in left hippocampal CA3 field in the young tremor rat, and then the spike and wave complex developed to bilateral corteces and right hippocampal CA3 area with aging.(2) The profile of the conventional antiepileptic drugs on the absence-like seizures was similar to that on human absence seizures, as in spontaneously epileptic rat (SER) : The seizure was inhibited by ethosuximide, trimethadione, valproate and phenobarbital, but not by phenytoin.(3) In hippocampal slice preparation, long-lasting depolarization shift accompanying repetitive firing was induced by a single stimulation of the mossy fiber in CA3 pyramidal cells. The response was inhibited by Ca^<2+> antagonist, nicardipine, suggesting that there is an enhancement of Ca^<2+> current in hippocampal CA3 pyramidal cells probably due to Ca^<2+> channel abnormality.(4) Ca^<2+> current sensitive to nicardipine was obtained using acutely dissociated hippocampal cells.These results imply that tremor rat is useful for evaluation of the acute and chronic effects of antiepileptics and study on the mechanism underlying the absence-like seizures.