title: Effects of modafinil on sleep-wake cycles in larval zebrafish.
abstract: We describe, for the first time, the effects of the wakefulness-promoting drug modafinil on sleep and wakefulness in larval zebrafish. Modafinil is currently used to treat narcolepsy, hypersomnia, and shift-work disorder by increasing wakefulness. Tolerance and dependence are limited with modafinil use, differentiating it from common stimulants; however, the neural mechanisms of action of modafinil are still unknown. Zebrafish, a low-cost, prolific, and genetically tractable animal model, have recently become a key model in sleep research. Zebrafish express circadian rhythms, sleep homeostasis, and sleep pressure, and, in addition, respond to common hypnotics and stimulants in a manner similar to mammals. Therefore, in the current experiment we characterize the effects of modafinil on sleep-wake cycles in larval zebrafish as a first step to gaining further insight into the neural mechanisms underlying the effects of modafinil. We show that modafinil modulates sleep-wake activity in larval zebrafish in a manner consistent with what would be predicted from mammalian data. Modafinil increases wakefulness by lengthening wake-bouts, an effect that likely restricted to the night (lights-off). These results validate the use of zebrafish as an animal model for the study of sleep and provide a means for dissecting the neural mechanisms of modafinil, and, more broadly, sleep disorders.
authors: Department of Biomedical Engineering, School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
authors: Benjamín
authors: B
authors: Sigurgeirsson
authors: Haraldur
authors: H
authors: Thorsteinsson
authors: Hrönn
authors: H
authors: Arnardóttir
authors: Ingibjörg Thorn
authors: IT
authors: Jóhannesdóttir
authors: Karl Aegir
authors: KA
authors: Karlsson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D000077408:Modafinil; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil