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

进行了研究，以建立新发现的震颤大鼠（tm/tm）的生产和维护，表现出失神样癫痫发作和这种动物的药理学用途。(1)幼年震颤大鼠脑电棘波复合体可能集中于左侧海马CA 3区，随年龄增长棘波复合体向双侧皮层和右侧海马CA 3区发展。(2)常规抗癫痫药物对失神样发作的作用与人类失神发作相似，如自发性癫痫大鼠（SER）：乙琥胺、曲美双酮、丙戊酸盐和苯巴比妥可抑制癫痫发作，但苯妥英钠不能抑制癫痫发作。(3)在海马脑片制备中，长持续的去极化移位伴随着重复放电诱导由一个单一的刺激苔藓纤维在CA 3锥体细胞。Ca^<2+>拮抗剂尼卡地平可抑制该反应，提示海马CA 3区锥体细胞Ca^<2+>电流增强可能与Ca^<2+>通道异常有关。(4)用急性分离的海马细胞获得了尼卡地平敏感的Ca^<2+>电流，提示震颤大鼠可用于评价抗癫痫药物的急、慢性效应和研究失神样发作的机制。

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.