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Abstract

Based on the reviewed literature and the data presented in this paper, conclusions can be drawn with respect to the validity of the WAG/Rij strain of rats as a model for absence epilepsy in humans. The view that the WAG/Rij model has "face validity" is supported by the simultaneous presence of clinical and electroencephalographic signs characterizing absences in rat and humans, by the decrease in responsiveness during the presence of spike-wave discharges in both species, by the agreement between model and patient with respect to the preferential occurrences of spike-wave discharges at transitions in states of vigilance, by the corresponding modulation of spike-wave discharges by physical and mental activities in both and, finally, by the fact that in both humans and rats absence epilepsy is inherited. Against this view, however, argue two points. In rats, absences appear after puberty and are maintained during life, while in humans the seizures occur before puberty and then disappear or convert to more serious forms of epilepsy. The second point is the frequency difference of the spikes and waves in the discharge train: 8-10 Hz in the rat and 3 Hz in the human (though there are no a priori reasons why the frequency of spike waves in the burst must be the same in all species). The absence model also has predictive validity, based on pharmacological data that demonstrate the specificity of certain drugs as being effective in convulsive epilepsies and not in absence epilepsy. So far, all drugs affect spike-wave activity the same way in rats and humans, with lamotrigine being, perhaps, the only exception. Furthermore, sleep deprivation is a powerful provocation for the initiation of spike-wave discharges in both rats and humans. Potential explanations for the presence of absence seizures in rats have been found at the levels of activities in networks and nuclei; of neurons, membrane properties, and ion channels; of proteins and enzymes; and, finally, of genes and chromosomes. Further descriptions of the cellular processes can be found extensively in the literature (e.g., McCormick and Contreras, 2001) and those of the thalamo-cortico-thalamic network in this review as well as in others (Avanzini et al., 1999). Considering the extensive involvement of the phenomena under study with theoretical issues such as the relationship between sleep spindles and spike-wave discharges, and the origin of seizure activity, it can be concluded that the model also has construct validity as far as the present neurobiological theories holding for absence epilepsy in humans are concerned. The WAG/Rij model can therefore be recommended for continued use in evaluating antiepileptic drugs for monotherapy and polytherapy, as well as for the toxicological side effects of putative new antiabsence drugs.

Two Types of Seizures in Homocysteine Thiolactone-Treated Adult Rats, Behavioral and Electroencephalographic Study

“…Although there are numerous well-characterized genetic models of absence epilepsy developed in selected rodent strains (Sasa et al 1988;Walton et al 1996;Coenen and van Luijtelaar 2003), several pharmacological agents such as penicillin and pentylenetetrazole, c-hydroxy-butyric acid models have been mainly used for conversion of animals in absence state. Herein observed effects of D,L-homocysteine thiolactone are similar to those elicited by acute administration of increasing doses of pentylenetetrazole (Fisher 1989;Kostopoulos 2000).…”

Reticular nucleus-specific changes in α3 subunit protein at GABA synapses in genetically epilepsy-prone rats

“…Altered GABA A R function has been described in the cerebral cortex and thalamus of two inbred strains of rats that exhibit spontaneous spike and wave seizures and are recognized as genetic models of absence epilepsy: genetic absence epilepsy rats from Strasbourg (GAERS) and Wistar albino Glaxo/Rij (WAG/ Rij) rats (23)(24)(25)(26)(27). In GAERS rats, GABA A R anomalies appear to be specific to the RTN and can be identified in recordings from RTN cells as inhibitory postsynaptic currents (IPSCs) of increased amplitude and faster decay times (23), leading to unusually strong bursts of action potentials in the neurons (28).…”

Power Frequency Magnetic Fields Increase Cell Proliferation in the Mammary Gland of Female Fischer 344 Rats but Not Various Other Rat Strains or Substrains

“…WAG rats exhibit a characteristic feature, the spontaneous occurrence of spike wave paroxysms in brain electroencephalograms that makes this strain a valuable model for absence epilepsy [48]. In addition to epilepsy research, WAG rats are widely used in cancer research, including studies on gamma irradiation on induction of mammary carcinoma [49, 50].…”