Antiepileptic effects of exenatide in penicillin induced acute epilepsy model in rats

Abstract

Glucagon-like peptide-1 receptors are widely expressed in the brain and its association with nitric oxide is suggestive of its role in epilepsy. In this study, we investigated the effects of exenatide, a glucagon-like peptide-1 receptor agonist, on the epileptiform activity induced by penicillin injection. The study used 72 male Wistar albino rats in 9 groups. All groups except the last group which received only exenatide, received intracortical penicillin injection to induce epileptiform activity. Exenatide was intraperitoneally injected in II-IV groups, at doses of 50, 100, 200 μ g/kg, respectively. Sodium nitroprusside (SNP) and N ω -nitro-L-arginine methyl ester (L-NAME) were injected to the V-VIII groups either alone or with exenatide. Electrocorticography was recorded for 3 h. While administration of 200 μ g/kg exenatide reduced the frequency of epileptiform activity, 50 and 100 μ g/kg doses of exenatide were not effective. When the effective dose of exenatide and the SNP were injected together the spike frequency decreased significantly. When the effective dose of exenatide was given with L-NAME spike frequency significantly decreased only between 90 and 110 min. There was no statistically significant difference in terms of latency and amplitude between the experimental groups. Exenatide had an anticonvulsant effect in penicillin-induced acute epilepsy model which is possibly via nitric oxide and include another pathway since its effect was partially blocked by L-NAME and potentiated by SNP.