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

Abstract

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<0.001) blocked by CGP35348 in PTZ-induced seizures. Conclusion: In summary, our findings suggest that GABAB receptors may mediate the antiepileptic action of ghrelin in the hippocampus. Therefore, it is possible to speculate that ghrelin acts in the hippocampus to modulate seizures via GABA.

Keywords

• Ghrelin
• Hippocampus
• Epilepsy
• PTZ
• CGP35348