Pilocarpine-induced seizure susceptibility in rats following prenatal methylazoxymethanol treatment.

Several rodent models of cortical malformation are available for the study of cellular mechanisms associated with early-onset epilepsy, but few are associated with spontaneous seizures. We examined the effect of pilocarpine on the spontaneous seizure development and excitability of the CA1 pyramidal cells of rats after prenatal treatment with methylazoxymethanol (MAM). Pilocarpine induced status epilepticus (SE) onset latency was greater for normal rats than for MAM-treated rats. After several days of normal behavior following pilocarpine treatment, the duration of spontaneous seizures were greater in MAM-pilocarpine rats than in normal-pilocarpine rats. Compared with the normal rats, electrical stimulation of afferent fibers resulted in more robust population responses in the CA1 region in all groups. At interstimulus intervals of 30 and 70 ms, the MAM-pilocarpine rats displayed a decrease in paired pulse inhibition versus the conventional MAM rats. A loss of somatostatin- and parvalbumin-immunoreactive neurons was apparent in the normal-pilocarpine rats, MAM-pilocarpine rats, and conventional MAM rats. These results indicate that pilocarpine induces spontaneous seizures and hyperexcitability in MAM-pilocarpine rats.