Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity
Open accessAbstract
Orexins (also named hypocretins) are recently discovered neuropeptides made exclusively in the hypothalamus. Recent studies have shown that orexin cells located specifically in lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. Administration of orexin has been shown to stimulate food consumption, and orexin signaling in VTA has been implicated in intake of high-fat food. In self-administration studies, the orexin 1 receptor antagonist SB-334867 (SB) attenuated operant responding for high-fat pellets, sucrose pellets and ethanol, but not cocaine, demonstrating that signaling at orexin receptors is necessary for reinforcement of specific rewards. The orexin system is also implicated in associations between rewards and relevant stimuli. For example, Fos expression in LH orexin neurons varied in proportion to conditioned place preference (CPP) for food, morphine, or cocaine. This Fos expression was altered accordingly for CPP administered during protracted abstinence from morphine or cocaine, when preference for natural rewards was decreased and drug preference was increased. Additionally, orexin has been shown to be involved in reward-stimulus associations in the self-administration paradigm, where SB attenuated cue-induced reinstatement of extinguished sucrose- or cocaine-seeking. Although the specific circuitry mediating the effects of orexin on food reward remains unknown, VTA seems likely to be a critical target for at least some of these orexin actions. Thus, recent studies have established a role for orexin in reward-based feeding, and further investigation is warranted for determining whether function/dysfunction of the orexin system may contribute to the overeating associated with obesity. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
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Several neurotransmitters, hormones, and neuropeptides involved in homeostatic regulation of food intake have been implicated in the rewarding effects of food and drugs.
“Several neurotransmitters, including DA, cannabinoids, opioids, gamma-aminobutyric acid (GABA) and serotonin, as well as hormones and neuropeptides involved in homeostatic regulation of food intake, such as insulin, orexin, leptin, ghrelin, PYY, glucagon-like peptide-1 (GLP-1) have been implicated in the rewarding effects of food and drugs (Tables 1 and 2) (18–21).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [20]
Several neurotransmitters, including DA, cannabinoids, opioids and serotonin, as well as hormones and neuropeptides involved in homeostatic regulation of food intake such as insulin, orexin, leptin and ghrelin, have been implicated in the rewarding effects of food.
“Several neurotransmitters, including DA, cannabinoids, opioids and serotonin, as well as hormones and neuropetides involved in homeostatic regulation of food intake, such as insulin, orexin, leptin and ghrelin, have been implicated in the rewarding effects of food (Atkinson 2008;Cason et al 2010;Cota et al 2006).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Cason et al 2010
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- Authors
- Cason, A. M., Smith, R. J., Tahsili-Fahadan, P., Moorman, D. E., Sartor, G. C., & Aston-Jones, G.
- Affiliations
- Medical University of South Carolina (US)
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 100
- Issue
- 5
- Pages
- 419-428
- ISSN
- 0031-9384 (ISSN-L)
- PMC
- PMC2886173
- OpenAlex
- W2029119693
- Cited by
- 229
- References
- 91
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 12 · 2022: 8 · 2021: 10 · 2020: 15 · 2019: 16 · 2018: 13 · 2017: 13 · 2016: 13 · 2015: 20 · 2014: 20 · 2013: 20 · 2012: 26
- FWCI
- 9.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute on Drug Abuse (R37DA006214, F32DA023354, P50DA015369, R01DA017289)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- orexin, reward seeking, addiction, obesity, lateral hypothalamus, ventral tegmental area, orexin-1 receptor, SB-334867, food reward, self-administration, conditioned place preference, cue-induced reinstatement, morphine, cocaine, ethanol, overeating
- MeSH terms
- Orexins, Animals, Food Preferences, Humans, Hypothalamic Area, Lateral, Neuropeptides, Obesity, Reward, Behavior, Addictive, Receptors, Neuropeptide, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Orexin Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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