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 language | English |
|---|---|
| Pages (from-to) | 2489-2498 |
| Number of pages | 10 |
| Journal | Neuropharmacology |
| Volume | 62 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Jun 2012 |
| Externally published | Yes |
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Keywords
- Behavioral
- Elevated plus-maze
- GABA
- Glutamate
- Veratrine
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines. / Sugiyama, Azusa; Saitoh, Akiyoshi; Iwai, Takashi; Takahashi, Kou; Yamada, Misa; Sasaki-Hamada, Sachie; Oka, Jun Ichiro; Inagaki, Masatoshi; Yamada, Mitsuhiko.
In: Neuropharmacology, Vol. 62, No. 8, 06.2012, p. 2489-2498.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines
AU - Sugiyama, Azusa
AU - Saitoh, Akiyoshi
AU - Iwai, Takashi
AU - Takahashi, Kou
AU - Yamada, Misa
AU - Sasaki-Hamada, Sachie
AU - Oka, Jun Ichiro
AU - Inagaki, Masatoshi
AU - Yamada, Mitsuhiko
PY - 2012/6
Y1 - 2012/6
N2 - 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
AB - 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
KW - Behavioral
KW - Elevated plus-maze
KW - GABA
KW - Glutamate
KW - Veratrine
UR - http://www.scopus.com/inward/record.url?scp=84859711158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859711158&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2012.02.012
DO - 10.1016/j.neuropharm.2012.02.012
M3 - Article
VL - 62
SP - 2489
EP - 2498
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 8
ER -