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GABA in the Nucleus Accumbens Shell Participates in the Central Regulation of Feeding Behavior
Open accessAbstract
We have demonstrated previously that injections of 6,7-dinitroquinoxaline-2,3-dione into the nucleus accumbens shell (AcbSh) elicits pronounced feeding in satiated rats. This glutamate antagonist blocks AMPA and kainate receptors and most likely increases food intake by disrupting a tonic excitatory input to the AcbSh, thus decreasing the firing rate of a population of local neurons. Because the application of GABA agonists also decreases neuronal activity, we hypothesized that administration of GABA agonists into the AcbSh would stimulate feeding in satiated rats. We found that acute inhibition of cells in the AcbSh via administration of the GABA A receptor agonist muscimol or the GABA B receptor agonist baclofen elicited intense, dose-related feeding without altering water intake. Muscimol-induced feeding was blocked by coadministration of the selective GABA A receptor blocker bicuculline, but not by the GABA B receptor blocker saclofen. Conversely, baclofen-induced feeding was blocked by coadministration of saclofen, but was not affected by bicuculline. Furthermore, we found that increasing local levels of GABA by administration of a selective GABA-transaminase inhibitor, γ-vinyl-GABA, elicited robust feeding in satiated rats, suggesting a physiological role for endogenous AcbSh GABA in the control of feeding. A mapping study showed that although some feeding can be elicited by muscimol injections near the lateral ventricles, the ventromedial AcbSh is the most sensitive site for eliciting feeding. These findings demonstrate that manipulation of GABA-sensitive cells in the AcbSh can have a pronounced, but specific, effect on feeding behavior in rats. They also constitute the initial description of a novel and potentially important component of the central mechanisms controlling food intake.
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“Pharmacological control of the output from the NAc shell can also have profound effects on food consumption [312,313], as does surgical or chemical lesion of the nigrostriatal or mesolimbic DA pathways.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [313]
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Metadata
- Authors
- Stratford, T. R., & Kelley, A. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-06-01
- Volume
- 17
- Issue
- 11
- Pages
- 4434-4440
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573549
- OpenAlex
- W1488496267
- Cited by
- 404
- References
- 51
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 6 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 15 · 2014: 17 · 2013: 18 · 2012: 25
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (R01DA004788, DA-04788, R37DA004788)
- 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 › Neuroscience and Neuropharmacology Research
- Keywords
- GABA, nucleus accumbens shell, feeding behavior, food intake regulation, muscimol, baclofen, GABAA receptor, GABAB receptors, vigabatrin, GABA transaminase
- MeSH terms
- Animals, Baclofen, Eating, Enzyme Inhibitors, Feeding Behavior, gamma-Aminobutyric Acid, Male, Microinjections, Muscimol, Nipecotic Acids, Nucleus Accumbens, Proline, Rats, Sprague-Dawley, GABA Agonists, GABA Antagonists, Vigabatrin, Rats
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