Biol. Pharm. Bull. 28(8) 1408—1413 (2005)

quency of cortical malformations in childhood epilepsy. However, very little is knownregarding the pathophysiological mechanisms of epileptogenicity in the malformed cortex, partly because of the rarity of experimental studies with animal models. In rats, the application of methylazoxymethanol (MAM) in utero (E15) results in the formation of dysplastic regions in the neocortex and the CA1 region of the hippocampus, as well as in the heterotopic clusters of neurons in the subcortical white matter. Some MAM-treated pups, with both neocortical and hippocampal dysgenesis, have a lower threshold for seizure activity. Heterotopic neurons in the MAM model lack potassium channels and exhibit burster firing properties and heterotopia received abundant GABAergic innervations in the MAM exposed rats. Heterotopic CA1 pyramidal neurons appear to have atypical electrophysiological and morphological characteristics and may form abnormal connections with neocortical regions. Although it is well established that these models mimic the structural aspects of human early-onset epilepsy syndrome, there were few behavioral changes regarding spontaneous and recurrent seizures in the MAM rats. When MAM animals were examined specifically for spontaneous seizures, no activity was detected, although some EEG and sleep-cycle irregularities exist. Behavioral changes are considered to be important factors in evaluating the usefulness of epilepsy animal models. Spontaneous electrographic and behavioral seizures have been observed in pilocarpine-induced status epilepticus (SE), although spontaneous epileptic seizures have not yet been observed in MAM-exposed rats. This indicates that the MAM rats were resistant to the development of spontaneous and recurrent seizures. Since spontaneous and recurrent seizures are typical characteristics of epilepsy, developing a similar seizure model in the MAM rats is important in the study of pathophysiological mechanisms that contribute to epileptogenesis. In the present study, we examined the facilitated effect of MAM-treated animals on seizure induced by pilocarpine.