Caffeine Delays Light-entrained Activity and Potentiates Circadian Photic Phase-resetting in Mice.

Caffeine is widely used to reduce sedation and increase alertness. However, long-term caffeine use may disrupt circadian (daily, 24-h) rhythms and thereby negatively affect health. Here, we examined the effect of caffeine on photic regulation of circadian activity rhythms in mice. We found that entrainment to a standard 12-h light, 12-h dark (LD) photocycle was delayed during oral self-administration of caffeine. Both acute, high-dose caffeine and chronic, oral caffeine exposure potentiated photic phase-delays in mice, suggesting a possible mechanism by which entrainment to LD was delayed. The effect of caffeine on photic phase-resetting was mimicked by administration of adenosine A1, but not A2A, receptor antagonist in mice. Our results support the hypothesis that caffeine interferes with the ability of the circadian clock to respond normally to light.