In rats that had already developed epilepsy, blocking the brain's ghrelin receptors with the compound D‑Lys‑3‑GHRP‑6 made seizures last longer and even triggered continuous seizure activity (status epilepticus). This suggests that the natural hormone ghrelin may help keep seizures in check.

Studies have shown the anti-seizure properties of the ghrelin hormone in different models of epilepsy. Nevertheless, the role of the endogenous ghrelin is unknown in the electrical kindling model of epilepsy. In this study, we evaluated the effect of the antagonism of the ghrelin receptors in the brain of fully kindled rats. Adult male Wistar rats weighing 300 g were used. Animals were stereotaxically implanted with two uni-polar electrodes in the skull surface and a tri-polar electrode in the basolateral amygdala, and a guide cannula in the left lateral ventricle. Animals underwent a rapid kindling protocol. After showing three consecutive stages of five seizures, the animals were considered fully kindled. D-Lys-3-GHRP-6 (1, 50, and 100 μg/rat) was injected intracerebroventricularly (i.c.v.) in the kindled animals. Each rat was considered as its control and received a single dose of D-Lys-3-GHRP-6. Seizure parameters including after discharge duration (ADD), seizure stage (SS), stage four latency (S4L), and stage five duration (S5D) were recorded. The paired t test indicated a significant increase in seizure induction. D-Lys-3-GHRP-6 (1 μg/rat; i.c.v.) prolonged ADD in the kindled rats, significantly. D-Lys-3-GHRP-6 (50 and 100 μg/rat; i.c.v.) induced spontaneous seizures, which led to status epilepticus in the kindled rats. The results indicate that the antagonism of the ghrelin functional receptors prolongs seizures and induces status epilepticus in the kindling model of epilepsy, and propose that the endogenous ghrelin signaling has crucial antiepileptic properties.