Abstract
1. Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the Per gene expression accompanying a behavioural phase shift. 2. Brotizolam (0.5-10 mg kg -1) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. 3. Brotizolam (5 mg kg -1) significantly reduced the expression of Per1 and Per2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. 4. Injection of 8-OH-DPAT (5 mg kg -1) at subjective daytime induced similar phase advances with a reduction of Per1 and Per2 expression. Co-administration of brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced Per expression. 5. Both phase advance and rapid induction of Per1 and Per2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with brotizolam 5 mg kg -1. 6. The present results strongly suggest that reduction of Per1 and/or Per2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in brotizolamor 8-OH DPAT-induced phase advances and the reduction of Per gene expression. 7. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
| Original language | English |
|---|---|
| Pages (from-to) | 1739-1747 |
| Number of pages | 9 |
| Journal | British Journal of Pharmacology |
| Volume | 131 |
| Issue number | 8 |
| Publication status | Published - 2000 |
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Keywords
- Benzodiazepine
- Brotizolam
- Hamster
- Per genes
- Phase shift
- Suprachiasmatic nucleus
ASJC Scopus subject areas
- Pharmacology
Cite this
Inhibitory action of brotizolam on circadian and light-induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus. / Yokota, Shin Ichi; Horikawa, Kazumasa; Akiyama, Masashi; Moriya, Takahiro; Ebihara, Shizufumi; Komuro, Goyo; Ohta, Tatsuro; Shibata, Shigenobu.
In: British Journal of Pharmacology, Vol. 131, No. 8, 2000, p. 1739-1747.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibitory action of brotizolam on circadian and light-induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus
AU - Yokota, Shin Ichi
AU - Horikawa, Kazumasa
AU - Akiyama, Masashi
AU - Moriya, Takahiro
AU - Ebihara, Shizufumi
AU - Komuro, Goyo
AU - Ohta, Tatsuro
AU - Shibata, Shigenobu
PY - 2000
Y1 - 2000
N2 - 1. Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the Per gene expression accompanying a behavioural phase shift. 2. Brotizolam (0.5-10 mg kg -1) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. 3. Brotizolam (5 mg kg -1) significantly reduced the expression of Per1 and Per2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. 4. Injection of 8-OH-DPAT (5 mg kg -1) at subjective daytime induced similar phase advances with a reduction of Per1 and Per2 expression. Co-administration of brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced Per expression. 5. Both phase advance and rapid induction of Per1 and Per2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with brotizolam 5 mg kg -1. 6. The present results strongly suggest that reduction of Per1 and/or Per2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in brotizolamor 8-OH DPAT-induced phase advances and the reduction of Per gene expression. 7. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
AB - 1. Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the Per gene expression accompanying a behavioural phase shift. 2. Brotizolam (0.5-10 mg kg -1) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. 3. Brotizolam (5 mg kg -1) significantly reduced the expression of Per1 and Per2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. 4. Injection of 8-OH-DPAT (5 mg kg -1) at subjective daytime induced similar phase advances with a reduction of Per1 and Per2 expression. Co-administration of brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced Per expression. 5. Both phase advance and rapid induction of Per1 and Per2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with brotizolam 5 mg kg -1. 6. The present results strongly suggest that reduction of Per1 and/or Per2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in brotizolamor 8-OH DPAT-induced phase advances and the reduction of Per gene expression. 7. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
KW - Benzodiazepine
KW - Brotizolam
KW - Hamster
KW - Per genes
KW - Phase shift
KW - Suprachiasmatic nucleus
UR - http://www.scopus.com/inward/record.url?scp=0034531465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034531465&partnerID=8YFLogxK
M3 - Article
C2 - 11139454
AN - SCOPUS:0034531465
VL - 131
SP - 1739
EP - 1747
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 8
ER -