Feeding behavior in dopamine-deficient mice
Open accessAbstract
Mice that cannot make dopamine (DA), a condition caused by the selective inactivation of tyrosine hydroxylase in dopaminergic neurons, are born normal but gradually become hypoactive and hypophagic, and die at 3 weeks of age. We characterized the feeding and locomotor responses of these DA-deficient (DA−/−) mice to 3,4-dihyroxy- l -phenylalanine ( l -DOPA) to investigate the relationship between brain DA levels and these complex behaviors. Daily administration of l -DOPA to DA−/− mice stimulated locomotor activity that lasted 6 to 9 hr; during that time the mice consumed most of their daily food and water. The minimal dose of l -DOPA that was sufficient to elicit normal feeding behavior in the DA−/− mice also restored their striatal DA to 9.1% of that in the wild-type (WT) mice at 3 hr; then DA content declined to <1% of WT levels by 24 hr. This dose of l -DOPA induced locomotor activity that exceeded that of treated WT mice by 5- to 7-fold, suggesting that DA−/− mice are supersensitive to DA. Unexpectedly, DA−/− mice manifested a second wave of activity 24 to 48 hr after l -DOPA treatment that was equivalent in magnitude to that of WT mice and independent of DA receptor activation. The DA−/− mice approached, sniffed, and chewed food during this second period of activity, but they ate <10% of that required for sustenance. Therefore, DA−/− mice can execute behaviors necessary to seek and ingest food, but they do not eat enough to survive.
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Restoration of tyrosine hydroxylase gene expression using gene therapy rescued deficient feeding behavior in DA-deficient mice.
“Moreover, restoration of tyrosine hydroxylase gene expression using gene therapy was able rescue the deficient feeding behavior in these DA-deficient mice [303].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [303]
Dopamine deficient mice still have the capacity to consume food or water if these are directly delivered to their mouths.
“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., 1999
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- Authors
- Szczypka, M. S., Rainey, M. A., Kim, D. S., Alaynick, W. A., Marck, B. T., Matsumoto, A. M., & Palmiter, R. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Palmiter, Richard D.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-10-12
- Volume
- 96
- Issue
- 21
- Pages
- 12138-12143
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC18425
- OpenAlex
- W2041114226
- Cited by
- 242
- References
- 37
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 10 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 7 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 8 · 2013: 7 · 2012: 11
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- University of Washington
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD009172, 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 › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- dopamine deficiency, feeding behavior, L-DOPA, locomotor activity, hypophagia, striatal dopamine, food seeking, dopamine supersensitivity
- MeSH terms
- Animals, Behavior, Animal, Brain, Carbidopa, Dopamine, Dose-Response Relationship, Drug, Feeding Behavior, Levodopa, Mice, Inbred C57BL, Motor Activity, Time Factors, Dopamine Agents, Receptors, Dopamine D1, Receptors, Dopamine D2, Mice, Dopamine D2 Receptor Antagonists
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