SUPPRESSION OF CORTICAL EPILEPTIC AFTERDISCHARGES IN DEVELOPING RATS BY ANTICONVULSANTS INCREASING GABAERGIC INHIBITION

The anticonvulsant action of three drugs facilitating GABAergic inhibi tion by different mechanisms (valproate, phenobarbital and progabide) was studied in 229 young rats (12, 18 and 25 days old) with implanted electrodes. Epileptic afterdischarges (ADs) elicited by electrical sti mulation of the sensorimotor cortex were used as a model. All three dr ugs were able to suppress ADs, even the lowest doses used blocked the prolongation seen with repeated stimulations under control conditions. In addition to these general effects, some differences among the thre e drugs were observed: phenobarbital (10, 20, and 40 mg/kg i.p.) exhib ited marked anticonvulsant action in all three age groups whereas valp roate (200 and 400 mg/kg i.p.) was somewhat less effective in the youn gest rats studied than in the two older groups. Progabide exhibited an effect similar to valproate when a higher dose (150 mg/kg i.p.) was t aken into account, but the lower dose (75 mg/kg i.p.) was most efficie nt in 12 day old rat pups. Our data support the possibility that corti cal ADs represent a model of human myoclonic seizures. In addition, th ey suggest an uneven development of individual components of the GABAe rgic inhibitory system.