Rat Model Of Absence Epilepsy Research Articles

Some solvents for antiepileptics have proepileptic potencies in the WAG/Rij rat model for absence epilepsy

Some solvents for antiepileptics were tested, for 4 consecutive days, in a rat model (the WAG/Rij inbred strain) for absence epilepsy. Electroencephalogram registrations and behavioral observations suggested that both Tween-80 and a mixture of saline/ethanol/propylene glycol caused an increase in the number of epileptic phenomena. This increase was not significant and restricted to injection day 1 with Tween-80 but was significantly present during all 4 injection days with the saline/ethanol/propylene glycol mixture. Furthermore, with this latter solvent the increase became larger during consecutive days. Because of the proepileptic potencies and the differential time effects of these solvents, their usage should be seriously questioned.

CNQX, a new non-NMDA receptor antagonist, reduces spike wave discharges in the WAG/Rij rat model of absence epilepsy

The effects on seizures, EEG and behavior of the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), were studied in the WAG/Rij rat with absence epilepsy. Intracerebroventricular injections (10, 50, and 100 nmol/5 μl CNQX) showed that CNQX decreases the number of spike wave discharges in a dose-dependent way. Coinjection of CNQX (100 nmol/5μJ) and AMPA (0.1 pmol/5 μl), kainic acid (0.01 nmol/5 μl) or NMDA (50 pmol/5 μl) attenuated the CNQX response, indicating that CNQX acts on both non-NMDA and NMDA receptors. The observed effects appear to be specific manipulations of the epilepsy not mediated by behavioral changes.

Anticonvulsant and sleep-waking influences of riluzole in a rat model of absence epilepsy

Six WAG/Rij rats, an animal model of human absence epilepsy, were injected intraperitoneally with riluzole. At 4 mg/kg, riluzole decreased the number, mean duration and spike-frequency of the spontaneously occurring discharges for 3 h. Riluzole also increased slow wave sleep at the expense of waking. As riluzole at 3 mg/kg decreased the number and spike-frequency of the discharges without inducing a sedative effect, this compound could be of therapeutic interest in human absence epilepsy.

Absence epilepsy and the level of vigilance in rats of the WAG/Rij strain

In man, a relationship exists between sleep-wake states and absence epilepsy. During wakefulness, spike-wave discharges predominantly occur when the level of vigilance is not high, while during sleep they have a preference to occur during slow-wave sleep. During this latter type of sleep, spike-wave discharges prevail in periods where slow-wave sleep is light. In a series of experiments, the WAG/Rij rat model for absence epilepsy was characterized with respect to the relationships between the level of vigilance, sleep-wake states and the occurrence of spike-wave discharges. In the first experiment, continuous recordings were made for a period of 48 h and a clear circadian rhythm was established for the number of spike-wave discharges. A maximum appeared during the middle of the dark period of the rat, whereas a minimum was detected directly after the onset of the light period, the time period during which deep slow-wave sleep predominates. The relationship of spike-wave discharges with states of vigilance was elaborated in a second study. Spike-wave discharges were mainly found during light slow-wave sleep, during passive wakefulness and in transition phases from sleep to wakefulness. During REM sleep no spike-wave discharges were found. In the last three experiments, the level of alertness was enhanced by various procedures as photostimulation, a learning task and deprivation of REM sleep. In all cases, an increase of alertness decreased the amount of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitation of Spike-Wave Activity by the Hypnotic Etomidate in a Rat Model for Absence Epilepsy

The epileptogenic effect of the short-acting hypnotic agent etomidate was investigated in WAG/Rij rats. Animals of this inbred strain show spontaneous spike-wave discharges and are regarded as a model for absence epilepsy. A dose-dependent increase in the total amount of spike-wave activity was found, when etomidate was injected intraperitoneally in doses of 1, 2.5, 5 and 10 mg/kg. At a dose of 10 mg/kg, spike-wave activity appeared almost uninterruptedly. Beginning with a dose of 5 mg/kg, the morphology of the spike-wave complexes changed after the administration of the drug; spike frequency decreased dose dependently from about 8 till about 4 Hz at 10 mg/kg. During spike-wave activity, animals were motionless and, certainly at 10 mg/kg of etomidate, were unresponsive to stimuli. For surgical anesthesia, a still higher dose of etomidate is necessary (20 mg/kg). It is concluded that etomidate facilitates the generation of spike-wave activity in rats with spontaneous absence seizures, presumably through its GABA-mimetic action.

Development of tolerance to the anticonvulsant effect of valproate but not to ethosuximide in a rat model of absence epilepsy

Ethosuximide and valproic acid were tested for 4 and 2 weeks, respectively, in rats showing the spontaneous spike-wave syndrome. Ethosuximide suppressed the syndrome at plasma concentrations of 75–100 μg/ml. High doses of valproate (170 mg/kg i.p., t.i.d.), resulting in plasma concentrations of about 500 μg/ml, were necessary to suppress the syndrome, but signs of tolerance to the drug developed from day 5. Tolerance was confined to the number of spike-wave complexes, whereas the duration of the discharges was shortened to 60% of the control value, without there being signs of tolerance. It is assumed that increases in cerebral GABA, induced by the high concentration of valproate, counteracted the anti-absence effect of the drug in this model.

The WAG/Rij rat model for absence epilepsy: age and sex factors

The effects of age and sex on spontaneously occurring spike-wave complexes in rats of the WAG/Rij strain were studied in 2 experiments. In the first study, 3 independent groups of male rats were tested; the first group at 75 days old, the second at 140 days and the third at 245 days. In the second study, males as well as females were repeatedly tested at the ages of 75, 125 and 175 days. Both experiments indicated an increase with age in the number of spike-waves complexes and in the number of rats with absences. In the second experiment there were no differences detected between males and females at any of the ages. Similarities to and differences with human absence epilepsy are discussed and it is once more concluded that this particular inbred strain may be useful as an additional model of absence epilepsy.

The usefulness of EEG recordings in the study of brain-behaviour relationships

Periods in the electroencephalogram (EEG) that immediately precede the onset of spontaneous spike-wave discharges (SWD) were examined in WAG/Rij rat model of absence epilepsy. Precursors of SWD (preSWD) were classified based on the distribution of EEG power in delta–theta–alpha frequency bands as measured in the frontal cortex. In 95% of preSWD, an elevation of EEG power was detected in delta band (1–4 Hz). 73% of preSWD showed high power in theta frequencies (4.5–8 Hz); these preSWD might correspond to 5–9 Hz oscillations that were found in GAERS before SWD onset [Pinault, D., Vergnes, M., Marescaux, C., 2001. Medium-voltage 5–9 Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: in vivo dual extracellular recording of thalamic relay and reticular neurons. Neuroscience 105, 181–201], however, theta component of preSWD in our WAG/Rij rats was not shaped into a single rhythm. It is concluded that a coalescence of delta and theta in the cortex is favorable for the occurrence of SWD. The onset of SWD was associated with strengthening of intracortical and thalamo–cortical coherence in 9.5–14 Hz and in double beta frequencies. No features of EEG coherence can be considered as unique for any of preSWD subtype. Reticular and ventroposteromedial thalamic nuclei were strongly coupled even before the onset of SWD. All this suggests that SWD derive from an intermixed delta–theta EEG background; seizure onset associates with reinforcement of intracortical and cortico–thalamic associations.