Failure of carbamazepine to prevent behavioural 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 prior to stimulation, rats were given i.p. injections of either saline or a commonly used antiepileptic drug, carbamazepine (5H-dibenz[b, f]azepine-5-carboxamide; CBZ; 20 mg/kg). When tested 2 weeks later in a water maze, both the saline- and the carbamazepine-pretreated rats showed similarly a severe impairment in spatial learning compared to non-stimulated controls. Histological evaluation revealed that the pyramidal cell damage was (P < 0.05) milder in the carbamazepine-pretreated group in the CA1, but not the CA3c subfield. However, the number of somatostatin-immunoreactive neurons in both stimulated groups was reduced equally. 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 somatostatin-immunoreactive neuron loss or the spatial learning deficit after perforant pathway stimulation in rats. The result clearly differs from that obtained either with a GABA (gamma-aminobutyric acid)-enhancing drug and a novel antiepileptic, vigabatrin (4-amino-hex-5-enoic acid) or with a competitive NMDA (N-methyl-D-aspartate) receptor antagonist, CGP 39551 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid carboxyethylester) in the same test situation.
Lahtinen
H
H
Department of Neurology, University of Kuopio, Finland.
Ylinen
A
A
Lukkarinen
U
U
Sirviö
J
J
Miettinen
R
R
Riekkinen
P
P
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology*; D004558:Electric Stimulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000503:physiopathology / Q000517:prevention & control; D013226:Status Epilepticus / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D000927:Anticonvulsants; D002220:Carbamazepine