Orexin Signaling in the Ventral Tegmental Area Is Required for High-Fat Appetite Induced by Opioid Stimulation of the Nucleus Accumbens
Open accessAbstract
The overriding of satiety and homeostatic control mechanisms by cognitive, rewarding, and emotional aspects of palatable foods may contribute to the evolving obesity crisis, but little is known about neural pathways and mechanisms responsible for crosstalk between the “cognitive” and “metabolic” brain in the control of appetite. Here we show that neural connections between the nucleus accumbens and hypothalamus might be part of this link. Using the well known model of selective stimulation of high-fat intake induced by intra-accumbens injection of the μ-opioid receptor agonist d -Ala2- N -Me-Phe 4 -gly 5 -ol-enkephalin (DAMGO), we demonstrate that orexin signaling in the ventral tegmental area is important for this reward-driven appetite to override metabolic repletion signals in presatiated rats. We further show that accumbens DAMGO in the absence of food selectively increases the proportion of orexin neurons expressing c-Fos in parts of the perifornical hypothalamus and that neural projections originating in DAMGO-responsive sites of the nucleus accumbens make close anatomical contacts with hypothalamic orexin neurons. These findings suggest that direct accumbens–hypothalamic projections can stimulate hypothalamic orexin neurons, which in turn through orexin-1 receptor signaling in the ventral tegmental area and possibly other sites interfaces with the motivational and motor systems to increase intake of palatable food.
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Lateral hypothalamic neurons expressing orexin and other transmitters such as neurotensin provide modulatory input to midbrain dopamine neurons.
“Recent investigations show that lateral hypothalamic neurons expressing orexin ([77](#B77), [199](#B199)) and other transmitters such as neurotensin ([101](#B101), [107](#B107)) provide modulatory input to midbrain dopamine neurons”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [199]
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- Authors
- Zheng, H., Patterson, L. M., & Berthoud, H.-R.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Berthoud, Hans-Rudolf
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-10-10
- Volume
- 27
- Issue
- 41
- Pages
- 11075-11082
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672863
- OpenAlex
- W2074617349
- Cited by
- 248
- References
- 53
- Citations by year
- 2025: 3 · 2024: 10 · 2023: 4 · 2022: 12 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 13 · 2015: 24 · 2014: 21 · 2013: 19 · 2012: 25
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-47348, R01DK071082, DK071082, R01DK047348, P30DK072476)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- orexin signaling, ventral tegmental area, nucleus accumbens, mu-opioid receptor, DAMGO, high-fat diet, appetite regulation, perifornical hypothalamus, orexin-1 receptor, c-fos, satiety, obesity, food reward, neural circuits
- MeSH terms
- Orexins, Analgesics, Opioid, Animals, Appetite, Appetite Regulation, Dietary Fats, Male, Mice, Inbred C57BL, Neural Pathways, Neuropeptides, Nucleus Accumbens, Signal Transduction, Rats, Sprague-Dawley, Ventral Tegmental Area, Receptors, Neuropeptide, Mice, Knockout, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Intracellular Signaling Peptides and Proteins, Mice, Rats, Orexin Receptors
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