Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland

Masayuki Ikeda, Makoto Asai, Takahiro Moriya, Masami Sagara, Shojiro Inoué, Shigenobu Shibata

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Effects of methylcobalamin (methyl-B12), a putative drug for treating human circadian rhythm disorders, on the melatonin-induced circadian phase shifts were examined in the rat. An intraperitoneal injection of 1-100 μg/kg melatonin 2-h before the activity onset time (CT 10) induced phase advances of free-running activity rhythms in a dose-dependent manner (ED50 = 1.3 μg/kg). Injection of methyl-B12 (500 μg/kg) prior to melatonin (1 μg/kg) injection induced larger phase advances than saline preinjected controls, while the injection of methyl-B12 in combination with saline did not induce a phase advance. These results indicate amplification of melatonin-induced phase advances by methyl-B12. Pinealectomy abolished the phase alternating effect of methyl-B12, suggesting a site of action within the pineal gland. In fact, methyl-B12 significantly increased the content of melatonin in the pineal collected 2-h after activity onset (CT 14). In contrast, no difference in melatonin content was found at CT 10, indicating that the effect of methyl-B12 may be gated after the activity onset time when endogenous melatonin synthesis is known to increase. These results suggest that methyl- B12 amplifies melatonin-induced phase advances via an increase in melatonin synthesis during the early subjective night at a point downstream from the clock regulation.

    Original languageEnglish
    Pages (from-to)98-104
    Number of pages7
    JournalBrain Research
    Volume795
    Issue number1-2
    DOIs
    Publication statusPublished - 1998 Jun 8

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    Pineal Gland
    Melatonin
    Injections
    Chronobiology Disorders
    mecobalamin
    Intraperitoneal Injections
    Running

    Keywords

    • Circadian phase shift
    • High performance liquid chromatography
    • Melatonin
    • Methylcobalamin
    • Monoamine assay
    • Pineal gland
    • Rat
    • Vitamin B

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland. / Ikeda, Masayuki; Asai, Makoto; Moriya, Takahiro; Sagara, Masami; Inoué, Shojiro; Shibata, Shigenobu.

    In: Brain Research, Vol. 795, No. 1-2, 08.06.1998, p. 98-104.

    Research output: Contribution to journalArticle

    Ikeda, Masayuki ; Asai, Makoto ; Moriya, Takahiro ; Sagara, Masami ; Inoué, Shojiro ; Shibata, Shigenobu. / Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland. In: Brain Research. 1998 ; Vol. 795, No. 1-2. pp. 98-104.
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