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In the past decades, several mutant genes that encode ion channel subunit proteins or their functionally-related proteins have been identified in pedigrees of idiopathic epilepsy. To explore the pathogenesis and pathophysiology of epilepsy syndrome, the functional abnormalities of transmission in genetic animal models bearing the mutant genes identified in pedigrees of idiopathic epilepsy should be analyzed. In spite of these efforts, it is important to identify the most suitable genetic animal models for exploration of epileptogenesis and ictogenesis, as well as the development of novel antiepileptic drugs. In the literature on genetic epileptic animal models, there is no systematic discussion on how to assess the validation criteria for such models. In this review, we describe the validation criteria for genetic animal models of epilepsy.

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1 To elucidate possible mechanisms underlying the e ects of carbamazepine (CBZ), valproate (VPA) and zonisamide (ZNS) on neurotransmitter exocytosis, the interaction between these three antiepileptic drugs (AEDs) and botulinum toxins (BoNTs) on basal, Ca 2+ -and K + -evoked release of dopamine (DA) and serotonin (5-HT) were determined by microdialysis in the hippocampus of freely moving rats. 2 Basal release of monoamine was decreased by pre-microinjection of the syntaxin inhibitor, BoNT/C, but only weakly a ected by the synaptobrevin inhibitor, BoNT/B. Ca 2+ -evoked release was inhibited by BoNT/C selectively. K + -evoked release was reduced by BoNT/B predominantly and BoNT/C weakly. 3 Perfusion with low and high concentrations of CBZ and ZNS increased and decreased basal monoamine release, respectively. Perfusion with VPA increased basal 5-HT release concentrationdependently, whereas basal DA release was a ected by VPA biphasic concentration-dependently, similar to CBZ and ZNS. This stimulatory action of AEDs on basal release was inhibited by BoNT/ C predominantly. 4 Ca 2+ -evoked monoamine release was increased by low concentrations of CBZ, ZNS and VPA, but decreased by high concentrations. These e ects of the AEDs on Ca 2+ -evoked release were inhibited by BoNT/C, but not by BoNT/B. 5 K + -evoked monoamine release was reduced by AEDs concentration-dependently. The inhibitory e ect of these three AEDs on K + -evoked release was inhibited by BoNT/B, but not by BoNT/C, 6 These ®ndings suggest that the therapeutic-relevant concentration of CBZ, VPA and ZNS a ects exocytosis of DA and 5-HT, the enhancement of syntaxin-mediated monoamine release during resting stage, and the inhibition of synaptobrevin-mediated release during depolarizing stage.

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