Effect of GABA and glutamate on dentate gyrus in rats throughout lidocaine kindling

Previous studies in our laboratory have shown that a decrement in serum thyroid hormones in rats increases seizure susceptibility to lidocaine-kindled seizures and increments of excitability in the hippocampal dentate gyrus region (DG). Since the neuronal excitability depends on activity of glutamatergic and GABAergic pathways, we tested if GABA administration into DG of hypothyroid rats protects against lidocaine-kindling seizures and if glutamate administration into DG of euthyroid rats can increment susceptibility to lidocaine-kindling seizures. Wistar rats (260-340 g) were randomly assigned to one of two groups: control (CG) and hypothyroid (hyG). The hyG received 60 mg/kg daily of methimazole for four weeks. A cannula guide was implanted in all the animals in DG (AP:-3 mm; L:-l mm; DV:3 mm) for the administration of 1 μl of GABA (0.1 M) or glutamate (0.1 M) throughout the lidocaine kindling protocol. Lidocaine was injected daily in doses of 60 mg/kg, ip. The results show that GABA does not protect against lidocainekindling seizures on hyG, while glutamate increases the convulsant effect of lidocaine in CG. These results suggest that that the increment in excitability on DG depends more on glutamatergic than GABAergic activity.