title: SB-334867, an orexin receptor 1 antagonist, decreased seizure and anxiety in pentylenetetrazol-kindled rats.
abstract: Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist (SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol (PTZ)-kindled rats. Kindling was induced by repeated intraperitoneal (IP) injections of PTZ (32 mg/kg) with two-day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular (ICV) injections of SB-334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure-related behaviors were monitored for 30 min following PTZ administration. The anxiety-like behaviors were also assessed using elevated plus-maze in the first and last days of the study. The results revealed that ICV injection of SB-334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ-induced anxiety-like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders.
authors.affiliation: Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Azadi Sq., Mashhad, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Kordi Jaz
authors.affiliation: Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Azadi Sq., Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Moghimi
authors.affiliation: Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Azadi Sq., Mashhad, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Fereidoni
authors.affiliation: Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Azadi Sq., Mashhad, Iran.
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Asadi
authors.affiliation: Physiology-Pharmacology Research Center and Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Pistachio Co Street, Rafsanjan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shamsizadeh
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Azadi Square, Mashhad, Iran.|School of Pharmacy, Mashhad University of Medical Sciences, Azadi Square, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Roohbakhsh
mesh_terms: D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D064446:Orexin Receptors / Q000187:drug effects / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000517:prevention & control*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D014508:Urea; D010433:Pentylenetetrazole
keywords: anxiety; elevated plus-maze; epilepsy; kindling; orexin receptor; seizure