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 μg/kg, respectively. Sodium
nitroprusside (SNP) and Nω-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 μg/kg exenatide reduced the
frequency of epileptiform activity, 50 and 100 μg/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.