title: Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines.
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.
authors.affiliation: Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Saitoh
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwai
authors.forename: Kou
authors.initials: K
authors.lastname: Takahashi
authors.forename: Misa
authors.initials: M
authors.lastname: Yamada
authors.forename: Sachie
authors.initials: S
authors.lastname: Sasaki-Hamada
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Oka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inagaki
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*; D001569:Benzodiazepines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D019782:Riluzole; D003975:Diazepam