Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE

User menu

  • Log out
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log out
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
ARTICLE, Behavioral/Systems

Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness

Thomas E. Scammell, Ivy V. Estabrooke, Marie T. McCarthy, Richard M. Chemelli, Masashi Yanagisawa, Matthew S. Miller and Clifford B. Saper
Journal of Neuroscience 15 November 2000, 20 (22) 8620-8628; DOI: https://doi.org/10.1523/JNEUROSCI.20-22-08620.2000
Thomas E. Scammell
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ivy V. Estabrooke
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie T. McCarthy
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard M. Chemelli
2Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masashi Yanagisawa
2Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew S. Miller
3Cephalon, Inc., West Chester, Pennsylvania, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clifford B. Saper
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts,
4Program in Neuroscience, Harvard Medical School, Boston, Massachusetts
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Modafinil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which modafinil acts, we administered a range of doses of modafinil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos immunohistochemistry. To contrast modafinil-induced wakefulness with spontaneous wakefulness, we administered modafinil at midnight, during the normal waking period of rats. To determine the influence of circadian phase or ambient light, we also injected modafinil at noon on a normal light/dark cycle or in constant darkness. We found that 75 mg/kg modafinil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. This low dose of modafinil also increased the number of Fos-immunoreactive (Fos-IR) neurons in the lateral subdivision of the central nucleus of the amygdala. Higher doses increased the number of Fos-IR neurons in the striatum and cingulate cortex. In contrast to previous studies, modafinil did not produce statistically significant increases in Fos expression in either the suprachiasmatic nucleus or the anterior hypothalamic area. These observations suggest that modafinil may promote waking via activation of TMN and orexin neurons, two regions implicated in the promotion of normal wakefulness. Selective pharmacological activation of these hypothalamic regions may represent a novel approach to inducing wakefulness.

  • modafinil
  • tuberomammillary nucleus
  • lateral hypothalamic area
  • perifornical area
  • orexin
  • hypocretin
  • striatum
  • amygdala
  • suprachiasmatic nucleus
  • anterior hypothalamic area
  • Fos
  • dopamine
  • stimulant
  • narcolepsy
View Full Text
Back to top

In this issue

The Journal of Neuroscience: 20 (22)
Journal of Neuroscience
Vol. 20, Issue 22
15 Nov 2000
  • Table of Contents
  • Cover (PDF)
  • Index by author
Email

Thank you for sharing this Journal of Neuroscience article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness
Thomas E. Scammell, Ivy V. Estabrooke, Marie T. McCarthy, Richard M. Chemelli, Masashi Yanagisawa, Matthew S. Miller, Clifford B. Saper
Journal of Neuroscience 15 November 2000, 20 (22) 8620-8628; DOI: 10.1523/JNEUROSCI.20-22-08620.2000

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness
Thomas E. Scammell, Ivy V. Estabrooke, Marie T. McCarthy, Richard M. Chemelli, Masashi Yanagisawa, Matthew S. Miller, Clifford B. Saper
Journal of Neuroscience 15 November 2000, 20 (22) 8620-8628; DOI: 10.1523/JNEUROSCI.20-22-08620.2000
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • modafinil
  • tuberomammillary nucleus
  • lateral hypothalamic area
  • perifornical area
  • orexin
  • hypocretin
  • striatum
  • amygdala
  • suprachiasmatic nucleus
  • anterior hypothalamic area
  • fos
  • dopamine
  • stimulant
  • narcolepsy

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

ARTICLE

  • A Precise Retinotopic Map of Primate Striate Cortex Generated from the Representation of Angioscotomas
  • Differential Role of Mitogen-Activated Protein Kinase in Three Distinct Phases of Memory for Sensitization in Aplysia
  • Evidence for Long-Lasting Cholinergic Control of Gap Junctional Communication between Adrenal Chromaffin Cells
Show more ARTICLE

Behavioral/Systems

  • Enhancement of Signal-to-Noise Ratio and Phase Locking for Small Inputs by a Low-Threshold Outward Current in Auditory Neurons
  • Confocal Analysis of Reciprocal Feedback at Rod Bipolar Terminals in the Rabbit Retina
  • Feedforward Mechanisms of Excitatory and Inhibitory Cortical Receptive Fields
Show more Behavioral/Systems
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
(JNeurosci logo)
(SfN logo)

Copyright © 2023 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.