Chronic caffeine treatment disrupts the circadian rhythm in Drosophila

Abstract

Sleep is regulated by the homeostatic system and the circadian clock. The circadian clock governs the timing of sleep-wake cycles and the homeostatic mechanisms modulate the amount and depth of sleep. Caffeine intake promotes wakefulness in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on both circadian and homeostatic regulation of sleep. Furthermore, sleep changes with age and the impact of caffeine on age dependent sleep fragmentation is yet to be understood. Hence in the present study, we examined the effect of short exposure to caffeine on homeostatic sleep and age dependent sleep fragmentation in Drosophila. We further assessed the effect of prolonged exposure to caffeine on homeostatic sleep and circadian clock in Drosophila. The results of our study showed that short exposure to caffeine reduces sleep in flies and enhances sleep fragmentation with increasing age. On the other hand, prolonged caffeine exposure did not exert any significant effect on duration of sleep in mature flies. Nevertheless, prolonged caffeine ingestion decreased the morning and evening anticipatory activity in these flies indicating that it affects the circadian rhythm. These flies also exhibited phase delay in the clock gene timeless transcript oscillation and altered behavioral rhythm with either a longer free running period or arrhythmicity under constant darkness. In summary, the results of our studies showed that short exposure to caffeine increases the sleep fragmentation with age whereas prolonged caffeine exposure disrupts the circadian clock. Statement of SignificanceIn the present study, we assessed the effect of duration of caffeine intake on age dependent sleep fragmentation and circadian clock by using Drosophila as a model organism. We found that short exposure to caffeine reduced sleep and food intake in flies. It also increased the sleep fragmentation with age. On the other hand prolonged caffeine exposure did not affect the sleep and feeding indicating that these flies developed tolerance to caffeine. As in mammals, caffeine slows down the circadian clock in flies. Most importantly, prolonged caffeine treatment disrupted the circadian rhythm in Drosophila. Our studies provide new insights into the differential effect of duration of caffeine intake on circadian clock and sleep.