The Pharmacology of Wakefulness

Details

• Personal Author:
  Miller DB ; O'Callaghan JP
• Description:
  Being awake, alert, and able to function in our 24-7 world is a challenge in the face of the fatigue and sleepiness engendered by long work hours, unusual work schedules, sickness, and other factors. Development of effective treatments to combat fatigue and sleepiness requires an understanding of the neurobiology of wakefulness. In this brief review, we examine the neuroanatomical, neurochemical, and molecular basis of the wakeful state to provide a framework for understanding current and future pharmacologic approaches to modification of wakefulness. The spontaneously awake state can be defined as a natural state of vigilance or arousal differing from natural sleep in both behavior and neural activity. These differences have long intrigued researchers and largely have been characterized in the brain areas and neurochemical systems affecting the sleep and wake states. Many of the strategies for promoting the awake condition involve manipulation or modulation of specific neurochemical systems with the ultimate goal of enhancing wakefulness, diminishing sleepiness, or both. Wakefulness is an important cortical function that depends on the coordinated effort of multiple brain areas including the thalamus, hypothalamus, and basal forebrain to integrate and relay information from the brainstem to the cortex. Norepinephrine and serotonin-long considered arousal-enhancing transmitters as well as glutamate, acetylcholine, histamine, and the neuromodulators hypocretin-orexins and adenosine, are known to affect the signal transduction in these brain areas and initiate, promote, or enhance wakefulness. Use of molecular tools to evaluate the awake, asleep, and sleep-deprived state has revealed novel insights concerning the gene expression events associated with wakefulness. Understanding wakefulness at this level undoubtedly will contribute to the development of pharmacologic approaches to promote or enhance the wakeful state. We caution, however, that sleep may have a necessary, restorative function for the brain; therefore, prolonging wakefulness for long periods through artificial means could have unexpected and perhaps detrimental consequences on brain health. [Description provided by NIOSH]
• Subjects:
  Behavior Fatigue Occupational Health Safety Shift Work Schedule Sleep Sleep Initiation And Maintenance Disorders
• Keywords:
  Behavior-patterns Fatigue-properties Pharmacology Shift-work Shift-workers Sleep-deprivation Sleep-disorders Worker-health Workers
• ISSN:
  0026-0495
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  55
• NIOSHTIC Number:
  nn:20030989
• Citation:
  Metab Clin Exp 2006 Oct; 55(Suppl 2):S13-S19
• Contact Point Address:
  Diane B. Miller, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• Email:
  dum6@cdc.gov
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  Metabolism: Clinical and Experimental
• Supplement:
  2
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d6f1fa544aff59de3337c2ace1bc016e8ad66cdeb23c409d2cbd2ec7ef647aa6a25257de56233580d986417ef3ff43dc2f4f953a914b8130a358b366eebd5780
• Download URL:
  https://stacks.cdc.gov/view/cdc/191396/cdc_191396_DS1.pdf
• File Type:
  [PDF - 195.60 KB ]