Korean J Physiol Pharmacol.  2006 Oct;10(5):235-242.

Effects of Ethosuximide on the Pilocarpine Induced Seizure in Rat Model of Neuronal Migration Disorder

Affiliations
  • 1Department of Dental Pharmacology, College of Medicine, Kyungpook National University, Daegu, Korea. bjchoi@knu.ac.kr
  • 2Department of Pharmacology, College of Medicine, Kyungpook National University, Daegu, Korea.

Abstract

Cortical malformation-associated epileptic seizures are resistant to conventional anticonvulsant drugs. Relatively little research has been conducted on 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 ethosuximide (ETX) 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 the amplitude and number of population spikes, and paired pulse inhibition in response to stimulation of the commissural pathway. Pharmaco-resistance was tested by measuring seizure latencies after pilocarpine administration (320 mg/kg, i.p.) with and without pre-treatment with ETX. Pre-treatment with 300 mg of ETX significantly prolonged the latency to the status epilepticus (SE) in both control and MAM-treated groups. Pre-treatment with ETX 100mg and ETX 200 mg had little effect in MAM-exposed rats. However, ETX 200 mg prolonged the latency to the SE in control groups. Spontaneous field potential and secondary after-discharges were higher for MAM-treated rat in comparison with control rats injects with ETX. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard ETX assessed in vivo. These data suggest that ETX do not prolong seizure latencies in MAM-rats exposed to pilocarpine.

Keyword

Ethosuximide; Dysplasia; Methylazoxymethanol acetate; Epilepsy; Pilocarpine

MeSH Terms

Animals
Anticonvulsants
Brain
Epilepsy
Ethosuximide*
Methylazoxymethanol Acetate
Models, Animal*
Neuronal Migration Disorders*
Neurons*
Pilocarpine*
Rats*
Seizures*
Status Epilepticus
Anticonvulsants
Ethosuximide
Methylazoxymethanol Acetate
Pilocarpine
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