Establishment of long-term maintenance of the spontaneously epileptic rats and their pharmacological use

自发性癫痫大鼠（SER）是由震颤杂合子（tm/+）和zitter纯合子（zi/zi）交配而成的双突变体（zi/zi，tm/tm），在9-10周龄时出现强直性惊厥和失神样发作。本研究旨在建立获得SER长期维持和药理学有用性的方法。此外，还观察了SER、tremor、zitter和Kyo：Wistar大鼠脑内的儿茶酚胺水平与癫痫发作的关系，在常规室建立的适当环境中，SER的雄性和雌性的平均存活时间分别为16.5和15.7周，无明显的季节性差异，而无对照的Kyo：Wistar大鼠在20周龄前死亡。用含0.1%苯巴比妥的饲料喂养SER，可使雄性和雌性SER的平均存活时间分别延长至22.3和19.1周龄，强直性惊厥的发生率也降低。然而，在EEG记录上检查的失神样癫痫发作不受影响，与人类癫痫的临床效果一致。10-12周龄SER和zitter大鼠尾核多巴胺含量显著高于同龄震颤大鼠和Kyo：Wistar大鼠。10-12周龄SER和zitter大鼠丘脑-下丘脑、中脑、脑桥-延髓和小脑的去甲肾上腺素水平显著高于年龄匹配的震颤和Kyo：Wistar大鼠。然而，在5周龄的年轻SER、atter、tremor和Kyo：Wistar大鼠中，儿茶酚胺水平没有这种变化。在BN大鼠的回交研究中，发现zi基因的改变伴随着儿茶酚胺水平的改变。这些结果表明，减少多巴胺和去甲肾上腺素水平增加参与了在SER中看到的癫痫发作的外观。

Spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm) obtained by mating the tremor heterozygote rat (tm/+) with the zitter homozygote rat (zi/zi), shows both tonic convulsion and absence-like seizure after 9-10 weeks of ages. The study was carried out to establish the methods to obtain a long-term maintenance of the SER and pharmacological usefulness. In addition, catecholamine levels in the brain of the SER, tremor, zitter and Kyo:Wistar rats were also examined with relation to the epileptic seizures.The mean survival times of the male and female SER under the appropriate environments established in the conventional room were 16.5 and 15.7 weeks without much seasonal deviation, while the no control Kyo:Wistar rats died before 20 weeks of age. When the SER was fed with 0.1 % phenobarbital containing-pallets, the mean survival times of male and female SER were significantly prolonged to 22.3 and 19.1 weeks of age, respectively, and frequency of the tonic convulsion was also decreased. However, the absence-like seizure examined on the EEG recording was unaffected, being in line with the clinical effects in human epilepsy. The dopamine level was significantly higher in caudate nucleus of the SER and zitter rats aged 10-12 weeks than that of the age-matched tremor and Kyo:Wistar rats. In contrast, the noradrenaline level was significantly higher in thalamus-hypothalamus, midbrain, pons-medulla and cerebellum of the SER and zitter rats aged 10-12 weeks than that of the agematched tremor and Kyo:Wistar rats. However, there were no such alteration of the catecholamine levels among the young SER, atter, tremor and Kyo:Wistar rats aged 5 weeks. In the backcross study using BN rats, the changes of catecholamine levels were found to accompany with zi gene. These results suggest that the decreased dopamine and increased noradrenaline levels are involved in the appearance of epileptic seizures seen in the SER.