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 language | English |
|---|---|
| Pages (from-to) | 98-104 |
| Number of pages | 7 |
| Journal | Brain Research |
| Volume | 795 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 1998 Jun 8 |
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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 journal › Article
}
TY - JOUR
T1 - Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland
AU - Ikeda, Masayuki
AU - Asai, Makoto
AU - Moriya, Takahiro
AU - Sagara, Masami
AU - Inoué, Shojiro
AU - Shibata, Shigenobu
PY - 1998/6/8
Y1 - 1998/6/8
N2 - 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.
AB - 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.
KW - Circadian phase shift
KW - High performance liquid chromatography
KW - Melatonin
KW - Methylcobalamin
KW - Monoamine assay
KW - Pineal gland
KW - Rat
KW - Vitamin B
UR - http://www.scopus.com/inward/record.url?scp=0032496762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032496762&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(98)00262-5
DO - 10.1016/S0006-8993(98)00262-5
M3 - Article
C2 - 9622603
AN - SCOPUS:0032496762
VL - 795
SP - 98
EP - 104
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -