FAILURE OF CARBAMAZEPINE TO PREVENT BEHAVIORAL AND HISTOPATHOLOGICAL SEQUELS OF EXPERIMENTALLY-INDUCED STATUS EPILEPTICUS

Sustained electrical stimulation of the perforant pathway was used to induce long-lasting hippocampal seizures in conscious rats. One hour p rior to stimulation, rats were given i.p. injections of either saline or a commonly used antiepileptic drug, carbamazepine (5H-dibenz[b,f]az epine-5-carboxamide; CBZ; 20 mg/kg). When tested 2 weeks later in a wa ter maze, both the saline- and the carbamazepine-pretreated rats showe d similarly a severe impairment in spatial learning compared to non-st imulated controls. Histological evaluation revealed that the pyramidal cell damage was (P < 0.05) milder in the carbamazepine-pretreated gro up in the CA1, bur not the CA3c subfield, However, the number of somat ostatin-immunoreactive neurons in both stimulated groups was reduced e qually. Thus, at the dose of 20 mg/kg, which is a usual anticonvulsive dose in humans, carbamazepine seems to offer only partial protection against pyramidal cell damage, but no protection against the hilar som atostatin-immunoreactive neuron loss or the spatial learning deficit a fter perforant pathway stimulation in rats. The result clearly differs from that obtained either with a GABA (gamma-aminobutyric acid)-enhan cing drug and a novel antiepileptic, vigabatrin (4-amino-hex-5-enoic a cid) or with a competitive NMDA (N-methyl-D-aspartate) receptor ant ag onist, CGP 39551 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenenoic ac id carboxyethylester) in the same test situation.