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Cited by 58Sleep and Wakefulness ResearchNeurotransmitter Receptor Influence on BehaviorRegulation of Appetite and Obesity

Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone

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Katzman, Martin A., Katzman, Matthew P.·2022·Brain Sciences
DOI 10.3390/brainsci12020150PMC PMC8870430
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Abstract

Orexin peptides comprise two neuropeptides, orexin A and orexin B, that bind two G-protein coupled receptors (GPCRs), orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2). Although cell bodies that produce orexin peptides are localized in a small area comprising the lateral hypothalamus and adjacent regions, orexin-containing fibres project throughout the neuraxis. Although orexins were initially described as peptides that regulate feeding behaviour, research has shown that orexins are involved in diverse functions that range from the modulation of autonomic functions to higher cognitive functions, including reward-seeking, behaviour, attention, cognition, and mood. Furthermore, disruption in orexin signalling has been shown in mood disorders that are associated with low hedonic tone or anhedonia, including depression, anxiety, attention deficit hyperactivity disorder, and addiction. Notably, projections of orexin neurons overlap circuits involved in the modulation of hedonic tone. Evidence shows that orexins may potentiate hedonic behaviours by increasing the feeling of pleasure or reward to various signalling, whereas dysregulation of orexin signalling may underlie low hedonic tone or anhedonia. Further, orexin appears to play a key role in regulating behaviours in motivationally charged situations, such as food-seeking during hunger, or drug-seeking during withdrawal. Therefore, it would be expected that dysregulation of orexin expression or signalling is associated with changes in hedonic tone. Further studies investigating this association are warranted.

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  • Orexin is associated with memory processing, motivation, reward, and addiction, which have been described as behaviors that are affected by TBI.

    “Orexin is also associated with memory processing,113–116 motivation, reward,117 and addiction,118 which have been described as behaviors that are affected by TBI.9,119–123”

    From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [117]

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Cited by

Sorted by citations

Authors
Katzman, M. A., & Katzman, M. P.
Affiliations
Queen's University (CA)
Corresponding author
Katzman, Martin A.
ORCID
Katzman, Martin A.
Venue
Brain Sciences
Publisher
MDPI AG
Published
2022-01-24
Volume
12
Issue
2
Pages
150
ISSN
2076-3425 (ISSN-L)
DOI
10.3390/brainsci12020150
PMC
PMC8870430
OpenAlex
W4210762547
Cited by
58
References
4
Citations by year
2026: 15 · 2025: 20 · 2024: 12 · 2023: 7 · 2022: 4
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
orexin, orexin-A, orexin B, orexin-1 receptor, orexin receptor 2, hedonic tone, anhedonia, mood disorders, depression, anxiety, attention deficit hyperactivity disorder, addiction, reward, motivation, lateral hypothalamus, G protein-coupled receptors

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