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Vitamin B12 Promotes Sleep and
Modulates the Circadian Rhythm of
Sleep and Brain Temperature in Rats
Shojiro Inou , D.Sc. and Kazuki Honda, Ph.D.
Vitamin B 12 improves circadian rhythm sleep disorders in humans. Since little is known
for its underlying mechanism, we investigated sleep and brain temperature (Tbr)-modulatory
activity of four different analogs of vitamin B 12 by infusing into the third
ventricle of freely behaving male rats for a 10-h nocturnal period. Three doses (1, 10 and
100 nmol) of methylcobalamin (methyl-B 12 ) dose-dependently enhanced both rapid-eye-movement
(REM) sleep and non-REM sleep during the infusion period and further
induced fluctuations of circadian sleep-waking rhythm for two post-infusion days. The
time-course pattern of non-REM sleep and REM sleep was interrelated before and during
the drug infusion period but dissociated thereafter. The administration of 100 nmol
methyl-B 12 resulted in a significant reduction of Tbr during the dark period in phase with
the enhancement of sleep. Subsequently, significant fluctuations of circadian rhythm of
Tbr occurred over two consecutive days independently from sleep-waking rhythm: a
nocturnal elevation on the first post-infusion day followed by a diurnal reduction and a
nocturnal elevation on the second post-infusion day. Lower doses of methyl-B 12 exerted
little effect on Tbr. Two analogs, 5’-deoxyadenosylcobalamin and hydroxocobalamin, at
100 nmol induced similar but less effects on sleep, whereas another analog,
cyanocobalamin, at 100 nmol was ineffective. These results suggest that vitamin B 12
acutely induced an enhancement of sleep by a direct action on the sleep-regulatory
mechanisms, being accompanied by a reduction of Tbr, and that the drug further
mediated a modulation of circadian rhythm of sleep-wakefulness and Tbr via its
nonspecific action on the biological clock. (Sleep and Hypnosis 1999;1:98-104)
Keywords: brain temperature, circadian rhythm, intracerebroventricular infusion, methylcobalamin,
non-REM sleep, rat, REM sleep, vitamin B 12 |
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