Development and usefulness of aging model rat with epileptic seizures.

自发性癫痫大鼠（SER）是一种基因定义的双突变体（zi/zi, tm/tm），通过震颤杂合大鼠与震颤纯合大鼠交配获得，在没有外部刺激或轻微的敲击和声音刺激时表现出缺乏性和强直性癫痫发作。定量放射自显像技术的计算机分析显示，（^3H）QNB在SER纹状体中与毒蕈碱胆碱能（mACh）受体的特异性结合量高于对照动物。然而，SER对GABA_A和苯环利定受体的特异性结合与对照组没有差异。这些结果表明，mACh受体的功能亢进参与了SER癫痫发作的出现。当对苔藓纤维施加单一刺激时，在成熟SER的海马CA3锥体神经元中存在重复放电和去极化移位，其中癫痫已经完全发展。然而，在年轻的SER和没有任何癫痫发作的幼崽中，苔藓纤维的每次刺激只会引起一个spike。这些结果表明，SER的CA3锥体神经元在癫痫发作的同时变得异常兴奋。在SER中，一种新型的促血小板释放激素（TRH）相关类似物CNK-602A以剂量依赖的方式抑制缺乏性和强张性癫痫发作，并且该药物对两种癫痫发作的抑制作用可通过氟哌啶醇预处理而拮抗。CNK-602A增加了大脑中多巴胺的释放。与TRH相比，CNK-602A的抗癫痫作用更强，持续时间更长。此外，我们发现l -精氨酸是大脑大动脉中一氧化氮形成的生理前体。

Spontaneously epileptic rat (SER) is a genetically defined double mutant (zi/zi, tm/tm) obtained by mating the tremor heterozygous rat with the zitter homozygous rat, and exhibits both absence-like and tonic seizures without external stimuli or when mildly stimulated by tapping and sound. Computer analysis using quantitative autoradiographic technique revealed that the amount of the specific binding of (^3H)QNB to muscarinic cholinergic (mACh) receptors in the striatum of SER was more than that of control animals. However, the specific bindings to GABA_A and phencyclidine receptors of SER were not different from those of controls. These results suggested that hyperfunction of mACh receptors was involved in the appearance of seizures of SER. When a single stimulus was applied to the mossy fibers, there was repetitive firing and a depolarization shift in the hippocampal CA3 pyramidal neurons of the mature SER, in which seizures had fully developed. However, in young SER and littermates, which did not show any seizures, only a single spike was elicited with each single stimulation of the mossy fibers. These results indicated that CA3 pyramidal neurons of the SER became abnormally excitable in conjunction with the development of seizures. In the SER, a novel throtropin-releasing hormone (TRH) related analog, CNK-602A, suppressed absence-like and tonic seizures in a dose-dependent manner, and the inhibitory effects of the drug on both seizures were antagonized by pretreatment with haloperidol. CNK-602A increased the release of dopamine in the brain. The antiepileptic effects of CNK-602A were more potent and lasted longer than those of TRH. Furthermore, we showed that L-arginine was a physiological precursor for the formation of nitric oxide in the large cerebral arteries.