Vitamin B12 Promotes Sleep and Modulates the Circadian Rhythm of Sleep and Brain Temperature in Rats

In human patients with circadian rhythm sleep disorders, chronic administration of a vitamin B12 analog, a-(5,6d imethy lbenz imidazo ly l ) -Co-methy l cobamide (methylcobalamin, methyl-B12), may improve their desynchronized sleep-wake cycles to entrain a 24-h nycthemeral cycle (1-4). However, the central mechanism involved in this phenomenon remains unknown. In an attempt to investigate the mechanism, we undertook a series of animal experiments to analyze effects of vitamin B12 on the circadian clock of free-running rats (5-10). We also undertook experiments to analyze direct effects of vitamin B12 on sleep in freely behaving rats by means of our long-term intracerebroventricular (icv) infusion technique, which we originally developed to quantify physiological sleep-promoting activity of sleep substances (11). Since four different analogs of vitamin B12 such as cyanocobalamin (cyano-B12), 5,6-dimethylbenzimidazolyl cobamide coenzyme (5’-deoxyadenosylcobalamin, DBCC), hydroxocobalamin (hydroxo-B12) and methyl-B12 are registered, we conducted an experimental analysis of sleepVitamin B12 Promotes Sleep and Modulates the Circadian Rhythm of Sleep and Brain Temperature in Rats