GABAB Receptor Blockade Prevents Antiepileptic Action of Ghrelin in the Rat Hippocampus

Purpose: Ghrelin has been shown to have antiepileptic function. However, the underlying mechanisms by which, ghrelin exerts its antiepileptic effects are still unclear. In the present study; we investigated antiepileptic mechanism of ghrelin through GABAB receptors using CGP35348 (selective GABAB receptor antagonist). Methods: Male Wistar rats' hippocampi were bilaterally microinjected with the single dose or 10-day ghrelin (0.3 nmol/μl/side). CGP35348, GABAB receptor antagonist, (12.5 μg/μl/side) or saline injected into the dorsal hippocampus 20 minutes before ghrelin administration. Thirty min after ghrelin microinjection, a single convulsive dose of pentylenetetrazole (PTZ) (50 mg/kg) was injected intraperitoneally (i.p). Afterwards, seizure duration and total seizure score (TSS) were assessed for 30 minutes in all animals. Results: Our results demonstrated that acute and chronic intrahippocampal (i.h.) injection of ghrelin could significantly (p<0.001) attenuate the severity of seizures. Ghrelin 0.3 nmol/μl/side decreased duration of seizure significantly both in acute (p<0.001) and chronic (p<0.01) injections. The ghrelin antiepileptic effect was completely antagonized by GABAB blockade. The suppression of both duration and TSS induced by ghrelin in hippocampus was significantly (p