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Cited by 1,234Sleep and Wakefulness ResearchRegulation of Appetite and ObesityNeuroscience of respiration and sleep

Orexin A activates locus coeruleus cell firing and increases arousal in the rat

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Hagan, Jim J., Leslie, Ron A., Patel, Sara, Evans, Martyn L., Wattam, Trevor A., Holmes, Steve, Benham, Christopher D., Taylor, Stephen G. +13 more·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.19.10911PMC PMC17982
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Abstract

The localization of orexin neuropeptides in the lateral hypothalamus has focused interest on their role in ingestion. The orexigenic neurones in the lateral hypothalamus, however, project widely in the brain, and thus the physiological role of orexins is likely to be complex. Here we describe an investigation of the action of orexin A in modulating the arousal state of rats by using a combination of tissue localization and electrophysiological and behavioral techniques. We show that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexin A increases cell firing of intrinsic noradrenergic neurones. Orexin A increases arousal and locomotor activity and modulates neuroendocrine function. The data suggest that orexin A plays an important role in orchestrating the sleep-wake cycle.

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  • Orexin neurons are both necessary and sufficient for wakefulness.

    “Orexin neurons are both necessary and sufficient for wakefulness.”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [32]

    The Results (page not provided) show that administering orexin A to rats increased arousal during the second and third hours after dosing. This supports a narrower claim that the peptide can promote wakefulness, but the paper does not show that activating orexin neurons is sufficient for wakefulness or that those neurons are necessary for it. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Injecting orexin into the brain causes an increase in wakefulness.

    “If orexin is injected into the brain, it causes an increase in wakefulness.32,33”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [32]

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Cited by

Sorted by citations

Authors
Hagan, J. J., Leslie, R. A., Patel, S., Evans, M. L., Wattam, T. A., Holmes, S., Benham, C. D., Taylor, S. G., Routledge, C., Hemmati, P., Munton, R. P., Ashmeade, T. E., Shah, A. S., Hatcher, J. P., Hatcher, P. D., Jones, D. N. C., Smith, M. I., Piper, D. C., Hunter, A. J., Porter, R. A., & Upton, N.
Affiliations
Neuroscience Research, Biopharmaceutical Development, Analytical Sciences, and Department of Discovery Chemistry, Europe, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex, United Kingdom CM19 5AW
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-09-14
Volume
96
Issue
19
Pages
10911-10916
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.19.10911
PMC
PMC17982
OpenAlex
W2031462960
Cited by
1,234
References
2
Citations by year
2026: 37 · 2025: 28 · 2024: 28 · 2023: 25 · 2022: 28 · 2021: 29 · 2020: 30 · 2019: 39 · 2018: 45 · 2017: 39 · 2016: 31 · 2015: 35 · 2014: 46 · 2013: 54 · 2012: 63
FWCI
33.36
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Hertfordshire Research Archive (University of Hertfordshire) (acceptedVersion)
  • Middlesex University Research Repository (Middlesex University Of London) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
orexin-A, locus coeruleus, arousal, noradrenergic neurons, sleep-wake cycle, lateral hypothalamus, locomotor activity, neuroendocrine function, attentional state
MeSH terms
Orexins, Animals, Arousal, Behavior, Animal, Carrier Proteins, Corticosterone, Dose-Response Relationship, Drug, Electroencephalography, Electrophysiology, Immunohistochemistry, Locus Coeruleus, Male, Neuropeptides, Prolactin, Sleep, Growth Hormone, Time Factors, Rats, Sprague-Dawley, Maze Learning, Intracellular Signaling Peptides and Proteins, Rats

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