Caffeine governs molecular mechanism(s) on circadian rhythm and circadian clock gene expression

Caffeine is one of the most widely used psychoactive substances, and it induces the arousal in the CNS, but also disrupts the quality of sleep. Recent studies reported that caffeine can affect the circadian rhythm, which associates many aspects of physiology, energy metabolism, sleep and homeostasis. Therefore we examined the arousal effects of caffeine via behavioral test, and determined its effects on circadian rhythm by measuring clock gene and clock‐controlled gene expression in mice brain. Male C57BL/6 mice were randomly divided into control, three experimental groups treated with vehicle, caffeine and caffeine with adenosine, respectively. Before administration of caffeine, forced treadmill exercise was applied to mice inducing physiological fatigue. Balance beam test and foot fault test were used to evaluate the balance ability in subjected mice. Caffeine treatment reduced weight gain, suggesting physiological effect of caffeine to inhibit food intake. In addition, average time to cross beam and error number of foot slip after caffeine injection were decreased compared with control. A foot fault was defined as the misplacement of fore or hind foot, thus the foot fault number after caffeine treatment was reduced compared with control. There were differences in expression of circadian clock genes including Clock, Per2, Cry1, and Cry2 by caffeine injection. Thus, these results demonstrate that caffeine can alter circadian rhythm in mice by regulating circadian clock gene expression. Support or Funding Information NRF‐2013R1A2A2A01067169 to Y.H., NRF‐2014R1A1A3051724 to S.P., Republic of Korea.