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.
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In rodents, a single dose of riluzole produces clear anxiolytic effects in a dose-dependent manner without evidence of oversedation, amnesia or coordinative problems as seen with BDZs.
“In rodents, a single dose of riluzole produces clear anxiolytic effects in a dose-dependent manner (Sugiyama et al., 2012) without evidence of oversedation, amnesia or coordinative problems as seen with BDZs.”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Sugiyama et al., 2012
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- Authors
- Sugiyama, A., Saitoh, A., Iwai, T., Takahashi, K., Yamada, M., Sasaki-Hamada, S., Oka, J.-I., Inagaki, M., & Yamada, M.
- Affiliations
- Tokyo University of Science (JP)
- National Center of Neurology and Psychiatry (JP)
- Corresponding author
- Saitoh, Akiyoshi
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 62
- Issue
- 8
- Pages
- 2489-2498
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2022550311
- Cited by
- 38
- References
- 55
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour and Welfare
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- riluzole, anxiolytic-like effects, benzodiazepine adverse effects, diazepam, sodium channels, veratrine, anxiety models, elevated plus maze, light/dark test, ethanol-induced sleep, Y-maze
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Benzodiazepines, Diazepam, Exploratory Behavior, Male, Motor Activity, Anti-Anxiety Agents, Rats, Wistar, Riluzole, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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