The novel brain neuropeptide, orexin‐A, modulates the sleep–wake cycle of rats
Abstract
Orexin‐A is a novel neuropeptide initially isolated from hypothalamic extracts but now known to be present in fibres distributed throughout the rat CNS including many regions associated with sleep–wake regulation. The recognition of a particularly dense innervation of orexinergic nerves in the locus coeruleus, together with the observed increase in firing rate of locus coeruleus neurons following application of orexin‐A in vitro, further highlighted a potential involvement of the peptide in modulating the arousal state. The present study was undertaken to determine the effects of intracerebroventricularly (ICV) administered orexin‐A on the sleep–wake cycle of conscious rats using electroencephalographic and electromyographic recordings. When administered at the onset of the normal sleep period, orexin‐A (1, 10 or 30 μg/rat ICV) produced a dose‐dependent increase in the time rats spent awake during the second and third hours after dosing. The enhancement of arousal was accompanied by a marked reduction in paradoxical sleep and deep slow wave sleep at the highest dose. The latency to the first occurrence of paradoxical sleep was also prolonged. This overall profile of increased arousal and decreased paradoxical sleep is consistent with a high rate of firing of locus coeruleus neurons as would be expected to occur following ICV administration of orexin‐A. It is concluded that orexin‐A may play an important physiological role in regulating the sleep–wake state, a hypothesis considerably strengthened by the recently reported narcoleptic phenotype of prepro‐orexin (the precursor for orexin‐A) knockout mice.
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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 [33]
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 [33]
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- Authors
- Piper, D. C., Upton, N., Smith, M. I., & Hunter, A. J.
- Corresponding author
- Piper, David C.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2000-02
- Volume
- 12
- Issue
- 2
- Pages
- 726-730
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2068973973
- Cited by
- 351
- References
- 2
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 11 · 2015: 15 · 2014: 14 · 2013: 18 · 2012: 27
- FWCI
- 15.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- orexin-A, sleep-wake cycle, arousal, locus coeruleus, REM sleep, slow-wave sleep, neuropeptides, intracerebroventricular administration, narcolepsy, hypothalamus
- MeSH terms
- Orexins, Amino Acid Sequence, Animals, Carrier Proteins, Circadian Rhythm, Electroencephalography, Electromyography, Injections, Intraventricular, Locus Coeruleus, Male, Molecular Sequence Data, Neuropeptides, Sleep Stages, Wakefulness, Intracellular Signaling Peptides and Proteins, Rats
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