Suppression of cortical epileptic afterdischarges in developing rats by anticonvulsants increasing GABAergic inhibition.
The anticonvulsant action of three drugs facilitating GABAergic inhibition 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 stimulation of the sensorimotor cortex were used as a model. All three drugs 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 three drugs were observed: phenobarbital (10, 20, and 40 mg/kg i.p.) exhibited marked anticonvulsant action in all three age groups whereas valproate (200 and 400 mg/kg i.p.) was somewhat less effective in the youngest 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 taken into account, but the lower dose (75 mg/kg i.p.) was most efficient in 12 day old rat pups. Our data support the possibility that cortical ADs represent a model of human myoclonic seizures. In addition, they suggest an uneven development of individual components of the GABAergic inhibitory system.
Polásek
R
R
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Kubová
H
H
Slamberová
R
R
Mares
P
P
Vorlícek
J
J
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development; D003864:Depression, Chemical; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D018682:GABA Agents / Q000627:therapeutic use*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D010634:Phenobarbital / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D014635:Valproic Acid / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D018682:GABA Agents; C017985:progabide; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D005968:Glutamate Decarboxylase; D010634:Phenobarbital