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Dopamine Production in the Caudate Putamen Restores Feeding in Dopamine-Deficient Mice
Open accessAbstract
Dopamine-deficient (DD) mice cannot synthesize dopamine (DA) in dopaminergic neurons due to selective inactivation of the tyrosine hydroxylase gene in those neurons. These mice become hypoactive and hypophagic and die of starvation by 4 weeks of age. We used gene therapy to ascertain where DA replacement in the brain restores feeding and other behaviors in DD mice. Restoration of DA production within the caudate putamen restores feeding on regular chow and nest-building behavior, whereas restoration of DA production in the nucleus accumbens restores exploratory behavior. Replacement of DA to either region restores preference for sucrose or a palatable diet without fully rescuing coordination or initiation of movement. These data suggest that a fundamental difference exists between feeding for sustenance and the ability to prefer rewarding substances.
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“However, restoration of DA into the NAc in these studies was not sufficient to rescue normal feeding behavior, but this may have been due to an inability to anatomically restore gene expression throughout the entire NAc [304].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [304]
In the citing paper
“A salient result from these animal studies is that DA transduction in the central or lateral regions of the caudate putamen was sufficient to permanently rescue mice from the starvation that would occur inevitably without daily L-DOPA injections.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [304]
In the citing paper
“However, these mice still have the capacity to consume food or water if these are directly delivered to their mouths (Szczypka et al., 1999; 2001).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Szczypka et al., 2001
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Metadata
- Authors
- Szczypka, M. S., Kwok, K., Brot, M. D., Marck, B. T., Matsumoto, A. M., Donahue, B. A., & Palmiter, R. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Palmiter, Richard D
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 30
- Issue
- 3
- Pages
- 819-828
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2102590502
- Cited by
- 354
- References
- 57
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 6 · 2023: 10 · 2022: 12 · 2021: 18 · 2020: 15 · 2019: 13 · 2018: 17 · 2017: 15 · 2016: 23 · 2015: 17 · 2014: 12 · 2013: 14 · 2012: 26
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (5 P30 DK35816-14, P30DK035816)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD008121, HD-08121)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- dopamine deficiency, caudate-putamen, nucleus accumbens, tyrosine hydroxylase, gene therapy, feeding behavior, hypophagia, nest building behavior, exploratory behavior, sucrose preference, reward, dopamine replacement therapy
- MeSH terms
- Adenoviridae, Animals, Dopamine, Feeding Behavior, Female, Food Preferences, Immunohistochemistry, Levodopa, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Movement, Nesting Behavior, Nucleus Accumbens, Recombinant Proteins, Transduction, Genetic, Tyrosine 3-Monooxygenase, Dopamine Agents, Neostriatum, Dietary Sucrose, Mice
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