Introduction: Epilepsy is a neurological disorder, a condition in which due to a chronic frequent seizures epileptic convulsions repeatedly occur as epilepsy disease.. Orexin is a brain Peptide originated from postero- lateral hypothalamus neurons that their projections could be find in different areas such as the hippocampus and brain stem. ICV injection of Orexins (A and B) affect sleep and nutritional behaviors. The purpose of this study was to investigate the role of oxA antagonist on seizure behaviors of PTZ induced kindled rats. Methods and Materials: Stainless steel cannula were implanted into the left ventricles of the brain in two groups of male Wistar rats (n=7) by stereotaxic surgery. The experimental group received Orexin A antagonist (5µg/rat, ICV). The ccontrol group received vehicle (2 µl/rat, ICV) using peristaltic pump. For kindling, PTZ injections (32 mg/kg/IP) was repeated for 12 days 30 minutes after antagonist injections. Results: The results showed that administration of Orexin A receptor antagonist increases latent period of generalized seizures in PTZ kindled rats. Discussion and Conclusion: Considering the anticonvulsant activity of Orexin A antagonist we can suggest that this effect may be due to blockade of the orexinergic receptors located in the CA3 area of hippocampus. Naturally these receptors are under Orexinergic neurons projected from other areas of the brain such as hypothalamic structures. So, by results of this study we can propose the antiseizure effect of OrexinA antagonist in PTZ kindled animals. Keywords: Orexin, Seizure, OXA Receptor antagonist, kindling

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