The cerebral content of excitatory and inhibitory amino acids in rats following withdrawal of antiepileptic drugs.

The aim of the present study was to investigate the role of amino acids in the increased seizure susceptibility induced by withdrawal of antiepileptic drugs (AEDs). Fifty white Wistar rats treated with AEDs and 30 controls were used. The animals were previously exposed to the acoustic stimulus and only the non responsive were used. The administered AEDs were morphosuximide, ethosuximide, phenobarbital, valproate and gluthetimide. The treatment was discontinued after 2 weeks. The acoustic stimulation was repeated after 2-4 days of abstention. The animals were sacrificed and the amino acids glutamate, aspartate, GABA, glycine and serine were determined in the cortex and the brain stem. The withdrawal of AEDs induced seizure susceptibility in 71% of the rats treated with phenobarbital and in 76% of those receiving morphosuximide. A significant increase of glutamate levels was found in the brain stem following withdrawal of both morphosuximide and ethosuximide. The level of GABA was elevated in the brain stem after valproate and morphosuximide withdrawal. The increase of glutamate concentration can be correlated with the increased seizure susceptibility. The unexpected rise of the GABA level could be interpreted as a compensatory inhibitory mechanism.