Melatonin is Required for the Circadian Regulation of Sleep

The use of melatonin is controversial as a sleep/circadian rhythm therapeutic. This paper uses the genetic knockout of arylalkylamineN-acetyltransferase 2 (required for melatonin synthesis) in zebrafish to elucidate the role of melatonin in sleep regulation. Zebrafish mutants that lack melatonin have significantly longer latency to sleep and shorter sleep bouts than wild-type fish. In the absence of circadian cues the circadian regulation of sleep is abolished, yet other behavioral and molecular circadian rhythms are maintained. Taken together, these experiments show that melatonin functions downstream of the central circadian pacemakers to promote the timing of and maintenance of sleep in this model system.