Abstracts

Rationale: Ghrelin is a 28 amino acid-containing bioactive peptide that plays a significant role in various functions, such as in the modulation of appetite, energy and glucose homeostasis. Studies are also implicating this peptide in the pathogenesis of many diseases, namely growth hormone deficiency, obesity and myopathy. Ghrelin is a peptide that is predominantly produced in the stomach, however it is also produced in the brain. This hormone is known to be a natural ligand of the growth hormone secretagogue (GHS) receptor type 1a (GHS-R1a) of which the mRNA is abundantly expressed in various brain structures such as the hypothalamus and hippocampus. The role of ghrelin in the mechanisms of epileptic seizures is not well explored to date. There is currently only one study showing that ghrelin delayed the onset times of characteristic behavioural pentylenetrazole-induced seizure-related changes and reduced the duration of tonic generalised extension (Obay et al., 2007). No studies have been performed to date to study the role of ghrelin in limbic seizures, therefore making us the first to test the non-peptide selective agonist for the ghrelin receptor capromorelin, using the pilocarpine model. Methods: Freely moving Wistar rats underwent a 2 hour intrahippocampal microperfusion of the selective ghrelin receptor agonist capromorelin (1-10-20µM) or the ghrelin receptor antagonist D-Lys³-GHRP-6 (40µM) via a stereotactically implanted microdialysis probe. 10mM pilocarpine was subsequently co-administered intrahippocampally for 40 min. Behavioural changes that were indicative of seizure activity were scored following the initiation of pilocarpine administration. Results: Capromorelin dose-dependently suppressed pilocarpine-induced limbic seizures. The ghrelin receptor antagonist D-Lys³-GHRP-6 did not affect seizure severity. Conclusions: Our results propose that activation of the hippocampal ghrelin GHS-R1a receptors results in the attenuation of locally provoked limbic seizures. Therefore ghrelin may play a role in the suppression of limbic seizures and the GHS-R1a receptor may become a potential therapeutic target for temporal lobe epilepsy.