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Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models  

Kim, Si-Hyung (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University)
Choi, In-Sun (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University)
Cho, Jin-Hwa (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University)
Park, Eun-Ju (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University)
Jang, Il-Sung (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University)
Choi, Byung-Ju (Department of Dental Pharmacology, College of Dentistry, Kyungpook National University)
Kim, Hyun-Jung (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University)
Kim, Young-Jin (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University)
Nam, Soon-Hyeun (Department of Pediatric Dentistry, College of Dentistry, Kyungpook National University)
Publication Information
International Journal of Oral Biology / v.31, no.2, 2006 , pp. 33-43 More about this Journal
Abstract
Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs)on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor amplitude and numbers of population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5 mg/kg; phenytoin 40, 60 mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320 mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.
Keywords
Antiepileptic drug; Dysplasia; Methylazoxymethanol Acetate;
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