in epi mutant chickens, convulsants which decreased brain gamma aminobutyric acid(GABA) levels bar inhibiting glutamic acid decarboxylase(GAD) activity elicited spontanous convulsions at lower concentrations than that required by normal chickens. Also anticonvulsant effects against IPS induced seizures were exerted by substances which increased brain GABA levels. These findings would suggest that brain GABA levels in epi mutant chickens may be inherently lower than that of normal chickens and that the activity and/or concentrations of CAD may be reduced.
The levels of whale brain GABA in epi mutant chickens ware indeed lower than those of normal chickens and showed further reductions during IPS-induced seizures. However, these reduced GABA levels did not appear to be related to any inherent alterations in the enzymatic activities of the GABA-synthesizing enzyme, GAD, or the degrading enzyme, GABA-transaminase(T), since the activities of these enzymes in whole brain samples were similar in both epi mutant chickens and normal chickens.
The epileptiform seizures evoked in the epi mutant chickens by stroboscopic stimulation can be attenuated or abolished by phenobarbital, phenytoin, and primidone at plasma concentrations closely approximating those required to control grand mal seizures in humans. Ethosuximide, an agent of choice in therapy of pent mal seizures, was inactive. Trimethadione and valproic acid also reduce seizure susceptivility. Valproic acid is effective against a variety of seizure types in humans. Seizures are also blocked by diazepam, clonazepan, and Δ9-tetrahydrocannabinol.
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