Dopaminergic role in stimulant-induced wakefulness

Jonathan P. Wisor, Seiji Nishino, Ichiro Sora, George H. Uhl, Emmanuel Mignot, Dale M. Edgar

Research output: Contribution to journalArticle

Abstract

The role of dopamine in sleep regulation and in mediating the effects of wake-promoting therapeutics is controversial. In this study, polygraphic recordings and caudate microdialysate dopamine measurements in narcoleptic dogs revealed that the wake-promoting antinarcoleptic compounds modafinil and amphetamine increase extracellular dopamine in a hypocretin receptor 2-independent manner. In mice, deletion of the dopamine transporter (DAT) gene reduced non-rapid eye movement sleep time and increased wakefulness consolidation independently from locomotor effects. DAT knock-out mice were also unresponsive to the normally robust wake-promoting action of modafinil, methamphetamine, and the selective DAT blocker GBR12909 but were hypersensitive to the wake-promoting effects of caffeine. Thus, dopamine transporters play an important role in sleep regulation and are necessary for the specific wake-promoting action of amphetamines and modafinil.

Original languageEnglish (US)
Pages (from-to)1787-1794
Number of pages8
JournalJournal of Neuroscience
Volume21
Issue number5
StatePublished - Mar 1 2001
Externally publishedYes

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Keywords

  • Amphetamine
  • Caffeine
  • Dopamine
  • Hypocretin
  • Modafinil
  • Narcolepsy
  • Sleep-wake cycle

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Wisor, J. P., Nishino, S., Sora, I., Uhl, G. H., Mignot, E., & Edgar, D. M. (2001). Dopaminergic role in stimulant-induced wakefulness. Journal of Neuroscience, 21(5), 1787-1794.