Effects of Antiepileptic Drugs on Absence‐Like and Tonic Seizures in the Spontaneously Epileptic Rat, a Double Mutant Rat

Abstract

Electroencephalographic (EEG) studies were performed to examine the effects of several antiepileptic drugs (AEDS) on absence-like and tonic seizures in the spontaneously epileptic rat (SER: zi(zi), tm/tm,), a double mutant rat, which was obtained by mating the tremor heterozygous animals (tm/ +) with the zitter homozygous animals (zi/zi), 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 hippocampus using implanted electrodes. The SER showed paroxysmal and synchronized 5-7-Hz spike-wave-like complexes in both cortical and hippocampal EEG during the absence-like state, which was characterized by immobility and staring. The animal also exhibited tonic convulsion without external stimulation concomitant with low-voltage fast waves on cortical and hippocampal EEG. In some animals, sporadic low-amplitude spikes appeared in the low-voltage fast waves during tonic convulsion. the absence-like seizures were inhibited by trimethadione (100 mg/kg intraperitoneally, i.p.) and ethosuximide 100 mg/kg i.p.), whereas the tonic convulsion was not affected by these drugs. In contrast, phenytoin (20 mg/kg i.p.) inhibited the tonic seizures without affecting the absence-like seizures. Phenobarbital (10 mg/kg i.p.) and valproate (200 mg/kg i.p.) inhibited both seizures to a similar degree. These results suggest that the SER, with both absence-like and tonic seizures, is a useful model for evaluation of AEDS.

A New Frontier in Epilepsy: Novel Antiepileptogenic Drugs

“…SER shows both absence-like seizure and tonic convulsions characterized by 5 -7 Hz spikewave-like complexes and fast activities in cortical and hippocampal electroencephalography (EEG) 8 weeks after birth (50). A recent study has demonstrated that SERs lack the gene-encoding aspartoacylase (an enzyme that metabolizes N-acetyl-L-aspartate (NAA) into acetate and aspartate) (51) and attractin required for the formation of myelin in nerves (52).…”

NER Rat Strain: A New Type of Genetic Model in Epilepsy Research

“…Spontaneous seizures in particular may contribute to understanding the nature of human epilepsy. In fact, some animal models exhibit seizures that correspond to certain types of epileptic seizures in humans, and the effects of antiepileptic drugs (AEDs) have been evaluated reasonably, using these animals (1)(2)(3)(4). At present, only a few rat models which have spontaneous seizures are known: genetically epilepsy-prone rats (GEPR-3 and GEPR-9) (5); WAG/Rij (6); genetic absence-epilepsy rats from Strasbourg (GAERS) (7); a rat mutant with spontaneous limbic-like seizures (8); tremor rats (TRM) (9); and spontaneously epileptic rats (SER) (3,lO).…”

The Wakayama Epileptic Rat(WER), a New Mutant Exhibiting Tonic-clonic Seizures and Absence-like Seizures.

“…Most of these epileptic rats show a frequency ranging from 7 to 11 Hz of SWD, including Wistar strain related rats [7,24,25]. Although TRM and SER rats exhibit absence-like epilepsy, the frequencies of the epileptic discharges of the two strains are reported to be between 5 to 7 Hz [19,20,26]. The frequency of SWD in the affected WER rats ranged from 4 to 6 Hz.…”

“…The absence seizures of the SER strain are specifically suppressed by ethosuximide and only the tonic-clonic seizures of the same strain are suppressed by phenytoin [19]. Therefore, the SER strain is considered a useful animal model of human epilepsies [19,21]. The WER strain has been maintained through full-sib mating in order to establish a new inbred strain animal model for human epilepsy.…”