title: The voltage-gated sodium channel activator veratrine induces anxiogenic-like behaviors in rats.
abstract: In this study, we investigated the anxiogenic-like effects of systemically administered veratrine in rat models of anxiety. In the light/dark test, veratrine (0.6 mg/kg, s.c.) significantly and dose-dependently decreased the time rats spent in and the number of entries into a light box 30 min after administration, suggesting that veratrine increases anxiety-like behaviors. These findings were also supported by results from the elevated-plus maze test and the tail-swing behavior test. In addition, veratrine (0.6 mg/kg, s.c.) significantly increased the plasma concentration of corticosterone, an endogenous biomarker for anxiety, compared to vehicle. On the basis of these results, we conclude that veratrine induces anxiogenic-like behaviors in rats. The anxiogenic-like behaviors induced by veratrine (0.6 mg/kg, s.c.) were completely abolished by co-treatment with the typical benzodiazepine anxiolytic diazepam (1 mg/kg, s.c.), when assessed in the elevated-plus maze test. Similar results were obtained with co-treatment with riluzole (10 mg/kg, p.o.), which directly affects the glutamatergic system and has recently been suggested to have anxiolytic-like effects. In conclusion, this study provides evidence that systemically administered veratrine induces anxiogenic-like behaviors in rats. We propose the veratrine model as a novel pathological animal model to explore possible candidate drugs for anxiolytics.
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan. Electronic address: asaitoh@ncnp.go.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Makino
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Leo
authors.initials: L
authors.lastname: Gotoh
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Sugiyama
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ohashi
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan; Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tsukagoshi
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Oka
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo 187-8553, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D017208:Rats, Wistar; D014702:Veratrine / Q000494:pharmacology*; D061585:Voltage-Gated Sodium Channel Agonists / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D061585:Voltage-Gated Sodium Channel Agonists; D014702:Veratrine; D003975:Diazepam
keywords: Anxiety-like behaviors; Anxiolytics; Diazepam; Innate anxiety; Riluzole