[Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the...

Kindling model has been regarded as an experimental model for partial seizure with secondary generalized convulsion in human epilepsy. A number of pharmacological studies have been carried out to evaluate antiepileptic effects of conventional anticonvulsants on kindled seizures, mainly using amygdala kindled model. However, it is known that hippocampus is a more important site for human temporal epilepsy. It should therefore be considered appropriate to evaluate effects of antiepileptic drugs, not only on amygdaloid- but also on hippocampal-kindled seizures. In the present study, effects of chronically administered phenobarbital (PB) on amygdaloid- and hippocampal-kindled seizures were investigated. In the first session, cats were orally administered 6 mg/kg of PB for 15 days to obtain the serum level between 15 micrograms/ml and 25 micrograms/ml (optimal level for human epileptic seizure), then stimulation was carried out once a day for the following five days with suprathreshold stimulation intensity (100 microA higher than generalized seizure triggering threshold). For evaluation of drug efficacy, duration of afterdischarge and seizure severity were determined. After the end of session 1, session 2 started with 12 mg/kg of PB for 35-50 micrograms/ml serum level (subtoxic level) and continued in the same manner as stated above. PB was proved to be more effective for hippocampal- than for amygdaloid-kindled seizures. Generalized convulsions were easily suppressed in the level of 15-25 micrograms/ml and afterdischarge was totally suppressed in 33% of cats in the level of 35-50 micrograms/ml in the hippocampal-kindled group. However, amygdaloid-kindled seizures were more resistant to PB. It was difficult to suppress generalized convulsion in the level of 15-25 micrograms/ml, and total suppression of afterdischarge was extremely rare even in the higher serum level in amygdaloid-kindled cats. In addition, cats requiring a smaller number of stimuli to the completion of kindling tended to show more marked drug-resistance. Such tendency could be seen in both groups, although, more distinct in amygdaloid-kindled cats. Also evaluated were effects of PB on the secondary site kindled-seizures and it was shown that the potency of PB was less manifest in secondary site amygdaloid seizures than in primary site hippocampal seizures. These data show that the drug efficacy in the kindling model depends on the stimulated brain region as well as animals predisposition probably related to rapid acquisition of epileptogenesis. The intractability of temporal lobe epilepsy might be related to the site of epileptic focus and predisposition of patients as well.(ABSTRACT TRUNCATED AT 400 WORDS)