Effect of GABA modifying agents on electroshock seizure threshold in alloxan diabetic mice

ABSTRACT

The effect of different Gabaminergic manipulations on the minimal electroshock seizure threshold [MEST] [an index of brain excitability] were studied in alloxan-diabetic mice. Treatment of diabetic mice by clonazepam which potentiates central endogenous GABA neurotransmission, or by valproate which inhibits GABA catabolism, produced a greater rise in MEST than in normal mice. The i.v. injection of gluose in these animals produced marked hyperglycemia associated with increased brain GABA content and MEST. Seizures induced by isoniazid, which inhibits GABA formation, were delayed and attenuated in alloxan-diabetic mice. It is Concluded that diabetic hyperglycemia, partly by enhancing brain GABA formation and turnover, decreases the tendency to seizures and can potentiate anticonvulsants that act largely by Gabaminergic mechanisms