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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.
AuthorsBenjamín Sigurgeirsson, Haraldur Thorsteinsson, Hrönn Arnardóttir, Ingibjörg Thorn Jóhannesdóttir, Karl Aegir Karlsson
JournalZebrafish (Zebrafish) Vol. 8 Issue 3 Pg. 133-40 (Sep 2011) ISSN: 1557-8542 [Electronic] United States
PMID21882999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • modafinil
Topics
  • Animals
  • Behavior, Animal (drug effects)
  • Benzhydryl Compounds (pharmacology)
  • Central Nervous System Stimulants (pharmacology)
  • Circadian Rhythm (drug effects)
  • Sleep (drug effects)
  • Wakefulness (drug effects)
  • Zebrafish

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