Effects of conventional anticonvulsant drugs on generalized tonic-clonic seizures in Noda epileptic rats

• NER rats have infrequent primary generalized tonic-clonic epilepsy.
• We developed a method for screening drugs as AEDs without priming in juvenile NERs.
• The seizures were evoked by strong environmental stimuli against adult NERs.
• Phenobarbital (PB) and valproate (VPA) suppressed the not-primed seizures of the NERs in a dose-dependent manner.

SummaryNoda epileptic rats (NERs) present with clinico-pathological manifestations reminiscent of human generalized tonic-clonic epilepsy. Thus, this strain of rat has been a model of primary, generalized, tonic-clonic epilepsy. However, the infrequency of seizures in these rats makes the assessment of antiepileptic drugs (AEDs) difficult. Therefore, traditional AEDs have only been tested in NERs against audiogenic seizures evoked by weekly acoustic priming from 3 to 22 weeks of age or by using the kindling procedure in adult animals. Adult NERs are susceptible to changes in their environment, such as bedding replacement or unpleasant sensory stimuli. In the present study, traditional AEDs—phenobarbital (PB) and sodium valproate (VPA)—were evaluated against seizures evoked by strong environmental stimuli in mature NERs that had not been previously primed. The number of animals presenting with seizures decreased in a dose-dependent manner following administration of either PB (dose range 1.0–5.0 mg/kg) or VPA (50 and 100 mg/kg). Consequently, the utility of NERs as a model of generalized tonic-clonic epilepsy was confirmed. This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs.