| Project/Area Number |
61870106
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kyoto University |
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Principal Investigator |
SASA Masashi Kyoto university, Faculty of Medicine, Assciate Professor, 医学部, 助教授 (20025654)
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| Co-Investigator(Kenkyū-buntansha) |
SERIKAWA Tadao Kyoto University, Faculty of Medicine, Assciate Professor, 医学部, 助教授 (30025655)
YAMADA Junzo Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (90025651)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1987: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1986: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Epilepsy / Spontaneously epileptic rat / antiepileptic drug / Phenobarbital / EEG Absence-like seizure / 欠神様発作 / 強直性けいれん / フェニトイン / トリメサジオン / エトスキサミド / フェノバール / バルブロ酸 |
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| Research Abstract |
Electroencephalographic (EEG) studies were carried out to examine the effects of several antiepileptic drugs on absence-like and tonic seizures in th spontaneously epileptic rat (SER: zi/zi, Tm/tm), a double mutant rat, which was obtained by mating the zitter homozygous animals (zi/zi) with the tremor heterzygous animals (tm/+), and to determine whether the seizures in the SER correspond to human absence and tonic seizures. Spontaneous EEG was continuously recorded from the frontal cortex and hiuppocampus using implanted electrodes. The SER showed paroxismal and synchronized 5-7 Hz spike-wave complexes in both cortical and hippocampal EEG during the absence-like state, which was characterized by immobility and staring. The animal also exhibited tonic conbulsion without external stimulation concomitant with low-voltage fast waves on cortical and hippocampal EEG. The absence-like seizures were inhibited by trimethadione and ethosuximide, while the tonic convulsion was not affected by these drugs. In contrast, phenytoin inhibited the tonic seizures without affecting the absence-like seizures. Phenobarbital and sodium valproate inhibited both seizures in a similar degree. When food pellets containing 0.1 % of phenobarbital were given ad libitum to the SER from 7 weeks of age, the drug concentrations in plasma were maintained at level of 30-50 <micrn>g/ml in males and 30-70 <micrn>g/ml in females. Under these conditions, the tonic convulsion which occurred spontaneously without external stimuli was inhibited in the SER between the ages of 8 and 15 weeks, although the inhibition was not evident after that. Body weight increased matkedly in the SER given phenobarbital compared with the controls. prolonged survival was also seen in male SER, but not female SER, given phenobarbital. These results suggest that the SER, with both absence-like and tonic seizures, is a useful animal model for evaluation of antiepileptic dgurs.
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