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

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Wakefulness
Dopamine
Sleep
Orexin Receptors
Amphetamines
Dopamine Antagonists
Methamphetamine
Amphetamine
Eye Movements
Caffeine
Knockout Mice
Dogs
Genes
modafinil
Therapeutics

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.

Dopaminergic role in stimulant-induced wakefulness. / Wisor, Jonathan P.; Nishino, Seiji; Sora, Ichiro; Uhl, George H.; Mignot, Emmanuel; Edgar, Dale M.

In: Journal of Neuroscience, Vol. 21, No. 5, 01.03.2001, p. 1787-1794.

Research output: Contribution to journalArticle

Wisor, JP, Nishino, S, Sora, I, Uhl, GH, Mignot, E & Edgar, DM 2001, 'Dopaminergic role in stimulant-induced wakefulness', Journal of Neuroscience, vol. 21, no. 5, pp. 1787-1794.
Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. Journal of Neuroscience. 2001 Mar 1;21(5):1787-1794.
Wisor, Jonathan P. ; Nishino, Seiji ; Sora, Ichiro ; Uhl, George H. ; Mignot, Emmanuel ; Edgar, Dale M. / Dopaminergic role in stimulant-induced wakefulness. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 5. pp. 1787-1794.
@article{5db2e95eb3de4042b39b5c3c038725a3,
title = "Dopaminergic role in stimulant-induced wakefulness",
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.",
keywords = "Amphetamine, Caffeine, Dopamine, Hypocretin, Modafinil, Narcolepsy, Sleep-wake cycle",
author = "Wisor, {Jonathan P.} and Seiji Nishino and Ichiro Sora and Uhl, {George H.} and Emmanuel Mignot and Edgar, {Dale M.}",
year = "2001",
month = "3",
day = "1",
language = "English (US)",
volume = "21",
pages = "1787--1794",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "5",

}

TY - JOUR

T1 - Dopaminergic role in stimulant-induced wakefulness

AU - Wisor, Jonathan P.

AU - Nishino, Seiji

AU - Sora, Ichiro

AU - Uhl, George H.

AU - Mignot, Emmanuel

AU - Edgar, Dale M.

PY - 2001/3/1

Y1 - 2001/3/1

N2 - 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.

AB - 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.

KW - Amphetamine

KW - Caffeine

KW - Dopamine

KW - Hypocretin

KW - Modafinil

KW - Narcolepsy

KW - Sleep-wake cycle

UR - http://www.scopus.com/inward/record.url?scp=0035283399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035283399&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 1787

EP - 1794

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 5

ER -