Introduction: Anxiety disorders are the most common neuropsychiatric disorders that often have an etiology of chronic stress. Available treatments are not always successful and need more research to provide effective treatments. Orexins (type A and B) are hypothalamic neuropeptides. Orexinergic neurons are localized in postero-lateral hypothalamic and prifornical area. Their projections to monoaminergic and cholinergic nuclei in the brain stem indicate their involvement in anxiety mechanisms. Kindling is a process that gradually stimulates brain structures involving in epileptiform convulsions. The purpose of this research was investigating the relationship between orexin antagonist and anxiety in kindled rats. Methods: 14 male Wistar rats were divided in two groups. Control group (n=7) received vehicle solution and experimental group (n=7) received 3.5μg/rat of the OX-2 receptor antagonist (ICV route, 2 μl/rat using peristaltic pump). Cannula was fixed in the left ventricle of the brain using stereotaxic method and surgery. Injections were repeated 12 times every 48h. Kindling was induced by PTZ (IP injection) and after 60 min anxiety behavior was determined using elevated plus-maze test. Results: Administration of OX-2 antagonist in kindled rats significantly reduced the anxiety behaviors in elevated plus-maze test. Conclusion: Inspite of chemical kindling, inhibition of orexinergic systems, reduced anxiety that could be probably via blocking of orexinergic pathways from hypothalamus to areas involving in anxiety and emotions.

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