Chronic caffeine treatment disrupts the circadian rhythm in Drosophila

Abstract

AbstractThe circadian clock governs the timing of sleep-wake cycles as well as of other behavioural, physiological and metabolic processes. While the endogenous circadian clock mediates the timing of sleep, homeostatic mechanisms modulate the amount and depth of sleep. Evidence from previous studies showed that caffeine intake promotes wakefulness, whereas adult-stage specific caffeine treatment not only suppresses sleep but also delays the phase of circadian rhythm 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 circadian and homeostatic regulation of sleep. In the present study we examined the differential effect of acute and chronic caffeine treatment on sleep ontogeny as well as on circadian and homeostatic regulation of sleep in Drosophila. The results of our study showed that acute caffeine treatment reduces day and night sleep in mature flies through the homeostatic pathway whereas it reduced only the day sleep in young flies. Chronic caffeine treatment did not exert any significant effect on sleep in young flies. On the other hand, it delayed the timing of sleep in mature flies and in addition flies under higher caffeine concentration reduced the morning and evening anticipatory activity under 12 hour: 12 hour light: dark cycles. These flies also exhibited either a longer free running period or arrhythmicity under constant darkness. The results of our study showed that acute caffeine treatment suppresses sleep through the homeostatic pathway whereas prolonged caffeine treatment disrupts the circadian rhythm in mature flies.Statement of significanceIn the present study, we assessed the effect of caffeine on sleep ontogeny and circadian rhythm by using Drosophila as a model organism. We found that acute treatment of caffeine reduced sleep in both young and mature flies. Young flies were tolerant to chronic caffeine treatment whereas it affected the timing of sleep in mature flies. 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 effect of prolonged daily caffeine intake on circadian clock and sleep.