SERIKAWA Tadao Faculty of Medicine, Institute of Laboratory Animals, Associate Professor, 医学部, 助教授 (30025655)
YAMADA Junzo Faculty of Medicine, Institute of Laboratory Animals, Professor, 医学部, 教授 (90025651)
|Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1988: ¥4,400,000 (Direct Cost: ¥4,400,000)
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.