Inhibitory action of brotizolam on circadian and light-induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus

Shin Ichi Yokota, Kazumasa Horikawa, Masashi Akiyama, Takahiro Moriya, Shizufumi Ebihara, Goyo Komuro, Tatsuro Ohta, Shigenobu Shibata

    Research output: Contribution to journalArticle

    45 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)1739-1747
    Number of pages9
    JournalBritish Journal of Pharmacology
    Volume131
    Issue number8
    Publication statusPublished - 2000

    Fingerprint

    brotizolam
    Suprachiasmatic Nucleus
    Cricetinae
    8-Hydroxy-2-(di-n-propylamino)tetralin
    Light
    Injections
    Triazolam
    Gene Expression
    Sleep Initiation and Maintenance Disorders
    Melatonin
    Benzodiazepines
    Running
    Pharmaceutical Preparations

    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 journalArticle

    Yokota, SI, Horikawa, K, Akiyama, M, Moriya, T, Ebihara, S, Komuro, G, Ohta, T & Shibata, S 2000, 'Inhibitory action of brotizolam on circadian and light-induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus', British Journal of Pharmacology, vol. 131, no. 8, pp. 1739-1747.
    Yokota, Shin Ichi ; Horikawa, Kazumasa ; Akiyama, Masashi ; Moriya, Takahiro ; Ebihara, Shizufumi ; Komuro, Goyo ; Ohta, Tatsuro ; Shibata, Shigenobu. / Inhibitory action of brotizolam on circadian and light-induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus. In: British Journal of Pharmacology. 2000 ; Vol. 131, No. 8. pp. 1739-1747.
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    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.",
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    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

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    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.

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    KW - Per genes

    KW - Phase shift

    KW - Suprachiasmatic nucleus

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