Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens
Abstract
Ghrelin, a powerful orexigenic peptide released from the gut, stimulates feeding when injected centrally and has thus far been implicated in regulation of metabolic, rather than hedonic, feeding behavior. Although ghrelin's effects are partially mediated at the hypothalamic arcuate nucleus, via activation of neurons that co-express neuropeptide Y and agouti-related protein (NPY/Agrp neurons), the ghrelin receptor is expressed also in other brain sites. One of these is the ventral tegmental area (VTA), a primary node of the mesolimbic reward pathway, which sends dopaminergic projections to the nucleus accumbens (Acb), among other sites. We injected saline or three doses of ghrelin (0, 0.003, 0.03, or 0.3 nmol) into the VTA or Acb of rats. We found a robust feeding response with VTA injection of ghrelin, and a more moderate response with Acb injection. Because opioids modulate feeding in the VTA and Acb, we hypothesized that ghrelin's effects in one site were dependent on opioid signaling in the opposite site. The general opioid antagonist, naltrexone (NTX), injected into the Acb did not affect feeding elicited by ghrelin injection into the VTA, and NTX in the VTA did not affect feeding elicited by ghrelin injected into the Acb. These results suggest interaction of a metabolic factor with the reward system in feeding behavior, indicating that hedonic responses can be modulated by homeostatic factors.
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Ghrelin action directly within the VTA activates dopamine neurons, increases accumbens dopamine turnover, and increases food intake.
“In contrast, ghrelin action directly within the VTA appears to activate dopamine neurons, increase accumbens dopamine turnover, and increase food intake”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [116]
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- Authors
- Naleid, A. M., Grace, M. K., Cummings, D. E., & Levine, A. S.
- Affiliations
- University of Minnesota (US)
- Veterans Health Administration (US)
- University of Washington (US)
- Corresponding author
- Levine, Allen S.
- ORCID
- Levine, Allen S.
- Venue
- Peptides
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 26
- Issue
- 11
- Pages
- 2274-2279
- ISSN
- 0196-9781 (ISSN-L)
- OpenAlex
- W2053820421
- Cited by
- 409
- References
- 34
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 9 · 2023: 4 · 2022: 12 · 2021: 14 · 2020: 17 · 2019: 17 · 2018: 21 · 2017: 26 · 2016: 20 · 2015: 23 · 2014: 25 · 2013: 35 · 2012: 29
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Peptides (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute on Drug Abuse (DA-03999, R01DA003999)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK68384, P30 DK 50456, P30DK050456, P01DK068384)
- National Institute of Dental and Craniofacial Research (T32DE007288, T32-DE-07288)
- 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 › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, feeding behavior, ventral tegmental area, nucleus accumbens, mesolimbic reward pathway, opioid signaling, naltrexone, hedonic feeding, homeostatic regulation, dopaminergic pathways, orexigenic peptides
- MeSH terms
- Animals, Feeding Behavior, Male, Neuropeptide Y, Nucleus Accumbens, Signal Transduction, Rats, Sprague-Dawley, Peptide Hormones, Receptors, G-Protein-Coupled, Rats, Ghrelin, Receptors, Ghrelin
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