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 ofits role in epilepsy. In this study, we investigated the effects of exenatide, a glucagon-like peptide-1 receptor agonist, on theepileptiform activity induced by penicillin injection. The study used 72 male Wistar albino rats in 9 groups. All groupsexcept the last group which received only exenatide, received intracortical penicillin injection to induce epileptiformactivity. Exenatide was intraperitoneally injected in II-IV groups, at doses of 50, 100, 200 μg/kg, respectively. Sodiumnitroprusside (SNP) and Nω-nitro-L-arginine methyl ester (L-NAME) were injected to the V-VIII groups either alone orwith exenatide. Electrocorticography was recorded for 3 h. While administration of 200 μg/kg exenatide reduced thefrequency of epileptiform activity, 50 and 100 μg/kg doses of exenatide were not effective. When the effective dose ofexenatide and the SNP were injected together the spike frequency decreased significantly. When the effective dose ofexenatide was given with L-NAME spike frequency significantly decreased only between 90 and 110 min. There was nostatistically significant difference in terms of latency and amplitude between the experimental groups. Exenatide had ananticonvulsant effect in penicillin-induced acute epilepsy model which is possibly via nitric oxide and include anotherpathway since its effect was partially blocked by L-NAME and potentiated by SNP.