Modeling the effect of exogenous melatonin on the sleep-wake switch

According to the Centers for Disease Control and Prevention and the Institute of Medicine of the National Academies, insufficient sleep has become a public health epidemic. Approximately 50-70 million adults (20 years or older) suffer from some disorder of sleep and wakefulness, hindering daily functioning and adversely affecting health and longevity. Melatonin, a naturally produced hormone which plays a role in sleep-wake regulation, is currently offered as an over-the-counter sleep aid. However, the effects of melatonin on the sleep-wake cycle are incompletely understood. The goal of this modeling study was to incorporate the effects of exogenous melatonin administration into a mathematical model of the human sleep-wake switch. The model developed herein adds a simple kinetic model of the MT1 melatonin receptor to an existing model which simulates the interactions of different neuronal groups thought to be involved in sleep-wake regulation. Preliminary results were obtained by simulating the effects of an exogenous melatonin dose typical of over-the-counter sleep aids. The model predicted an increase in homeostatic sleep drive and a resulting alteration in circadian rhythm consistent with experimental results. The time of melatonin administration was also observed to have a strong influence on the sleep-wake effects elicited, which is also consistent with prior experimental findings.