Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines

Azusa Sugiyama, Akiyoshi Saitoh, Takashi Iwai, Kou Takahashi, Misa Yamada, Sachie Sasaki-Hamada, Jun Ichiro Oka, Masatoshi Inagaki, Mitsuhiko Yamada

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

In this study, we investigated the anxiolytic-like effect of riluzole using three different innate anxiety models in rats. In the elevated plus-maze test, riluzole significantly increased the time spent in, and entries into, the open arm after 60 min administration. This finding was supported by results obtained from light/dark and open-field tests. The magnitude of the anxiolytic-like effects of riluzole in each of the behavioral models was similar to those produced by a benzodiazepine, diazepam, suggesting that riluzole has a robust anxiolytic-like activity in rats. To clarify the involvement of sodium channels in this anxiolytic activity, we examined the effect of a co-administered sodium channel activator, veratrine. The anxiolytic-like action of riluzole was diminished by veratrine in the elevated plus-maze, light/dark and open-field tests. Based on these results, it is suggested that the anxiolytic mechanism of riluzole is clearly distinct from that of diazepam. In addition, to examine whether riluzole directly and non-selectively affected the GABA A-benzodiazepine receptor complex, we performed three behavioral tests (footprint analysis, Y-maze test and the ethanol-induced sleeping time test) that are closely related to the GABA A-benzodiazepine pathways. In contrast to diazepam, riluzole produced no significant effects in these tests. Here, we provide the first report demonstrating that riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines. Crown

Original languageEnglish
Pages (from-to)2489-2498
Number of pages10
JournalNeuropharmacology
Volume62
Issue number8
DOIs
Publication statusPublished - Jun 1 2012

Keywords

  • Behavioral
  • Elevated plus-maze
  • GABA
  • Glutamate
  • Veratrine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Sugiyama, A., Saitoh, A., Iwai, T., Takahashi, K., Yamada, M., Sasaki-Hamada, S., Oka, J. I., Inagaki, M., & Yamada, M. (2012). Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines. Neuropharmacology, 62(8), 2489-2498. https://doi.org/10.1016/j.neuropharm.2012.02.012