The voltage-gated sodium channel activator veratrine induces anxiogenic-like behaviors in rats

• Published in: Behavioural brain research 2015-10, Vol.292, p.316-322
• Main Authors: Saitoh, Akiyoshi, Makino, Yuya, Hashimoto, Tomio, Yamada, Misa, Gotoh, Leo, Sugiyama, Azusa, Ohashi, Masanori, Tsukagoshi, Mai, Oka, Jun-Ichiro, Yamada, Mitsuhiko
• Format: Article
• Language: English
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Anxiety - drug therapy; Anxiety-like behaviors; Anxiolytics; Behavior, Animal - drug effects; Diazepam; Diazepam - pharmacology; Exploratory Behavior - drug effects; Innate anxiety; Male; Maze Learning - drug effects; Motor Activity - drug effects; Rats, Wistar; Riluzole; Veratrine - pharmacology; Voltage-Gated Sodium Channel Agonists - pharmacology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.06.022

•Systemically administered veratrine induced anxiety-like behaviors in the rat light/dark test.•This finding was supported in the elevated-plus maze and tail-swing behavior tests.•Veratrine increased plasma corticosterone concentrations in rat.•Veratrine-induced anxiety-like behaviors were abolished by riluzole and diazepam.•This model is a novel pathological animal model for exploring possible candidate drugs for anxiolytics. In this study, we investigated the anxiogenic-like effects of systemically administered veratrine in rat models of anxiety. In the light/dark test, veratrine (0.6mg/kg, s.c.) significantly and dose-dependently decreased the time rats spent in and the number of entries into a light box 30min 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 (0.6mg/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 (0.6mg/kg, s.c.) were completely abolished by co-treatment with the typical benzodiazepine anxiolytic diazepam (1mg/kg, s.c.), when assessed in the elevated-plus maze test. Similar results were obtained with co-treatment with riluzole (10mg/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.