Effect of GABA modifying agents on seizure susceptibility in insulin hypoglycaemic mice

Insulin hypoglycaemia produced significant catalepsy, reduction in brain GABA content, and enhanced seizure susceptibility as evident by the reduction in the minimal electroshock seizure threshold [MEST]. These effects of insulin were dose-dependent, and were prevented by i. p. treatment with glucose [2 g/kg]. Enhancement of brain GABA content and/or neurotransmission by valproate [300mg/kg] or clonazpam [5 mg/kg] i.p., respectively, prevented the effect of insulin [2U/kg] hypoglycamia on the MEST but potentiated the catalepsy, while depletion of brain GABA content by subconvulsive dose of isoniazid [50 mg/ kg] further enhanced brain excitability in these animals inducing spontaneous convulsion Clonazepam partially corrected the hypoglycaemia, while valproate further reduced the blood glucose level, but isoniazid did not affect it significantly, lt is concluded that the increased seizure susceptibility during hypoglycaemia involves both lack of energy supply to neurones as well as reduction in GABA minergic neuronal inhibition. Clonazepam, and possibly other anticonvulsant benzodiazepines seem to be suitable alternatives to glucose in correcting both these factors, and more preferable to other antiepileptic agents in treating hypoglycaemic convulsions

Relation of brain GABA to variations in electroseizure threshold during hyperglycemia

Moderate hyperglycemia in alloxan-diabetic mice or following i.v. glucose injection in normal mice causes a non-significant elevation in brain GABA and minimal electro-shock seizure threshold [MST]. However severe hyperglycemia seen at 5 min following i.v. glucose in normal mice or at 1 hr after i.v. glucose in alloxan-diabetic mice produced a significant elevation of brain GABA, activity which was reflected in elevation of the MST and therefore a reduction in seizure susceptibility. It is concluded that hyperglycemia tends to elevate brain GABA activity but this becomes statistically significant in severe hyperglycemia. This may explain the reduced susceptibility and severity of seizures in some patients with diabetes mellitus