The role of Ghrelin in pilocarpine-induced limbic seizures

Ghrelin is an endogenous ligand of GHSR1a. Ghrelin's role in the mechanisms of epileptic seizures is not well explored to date. The aim of this study was to clarify the mechanism through which ghrelin exerts its anticonvulsant effect. Freely moving Wistar rats underwent intrahippocampal microperfusion of ghrelin, truncated ghrelin, a GHSR1a antagonist or inverse agonist via a stereotactically implcanted microdialysis probe prior to pilocarpine administration. Furthermore, male GHSR1a-/- (KO) and GHSR1a+/+ (WT) mice were compared for genotype differences in seizure thresholds via intravenous pilocarpine tail infusion. Seizure thresholds were determined for the stages of pilocarpine-induced behavioural changes. Ghrelin dose-dependently inhibited seizures in rats. Interestingly, both antagonist and inverse agonist also suppressed seizures. Truncated ghrelin, which is less able to desensitize GHSR1a than ghrelin, was not able to protect against seizures. Seizure thresholds in KO mice were higher compared to WT, which is in line with the results of the antagonist/inverse agonist. Thus GHSR1a is implicated in epilepsy. Blockage of the receptor is necessary to obtain an anticonvulsant effect and our results indicate that ghrelin may work on the GHSR1a through desensitization.