Dopamine is required for hyperphagia in Lepob/ob mice
Abstract
Feeding is a complex process responsive to sensory information related to sight and smell of food, previous feeding experiences, satiety signals elicited by ingestion and hormonal signals related to energy balance. Dopamine released in specific brain regions is associated with pleasurable and rewarding events and may reinforce positive aspects of feeding. Dopamine also influences initiation and coordination of motor activity and is required for sensorimotor functions. Thus, dopamine may facilitate integration of sensory cues related to hunger, initiating the search for food and its consumption. Dopaminergic neurons in the substantia nigra and ventral tegmental area project to the caudate putamen and nucleus accumbens, where they modulate movement and reward. There are projections from the nucleus accumbens to the lateral hypothalamus that regulate feeding. Dopamine-deficient mice (Dbh(Th/+), Th-/-; hereafter DD mice) cannot synthesize dopamine in dopaminergic neurons. They gradually become aphagic and die of starvation. Daily treatment of DD mice with L-3,4-dihydroxyphenylalanine (L-DOPA) transiently restores brain dopamine, locomotion and feeding. Leptin-null (Lep(ob/ob)) mice exhibit obesity, decreased energy expenditure and hyperphagia. As the hypothalamic leptin-melanocortin pathway appears to regulate appetite and metabolism, we generated mice lacking both dopamine and leptin (DD x Lep(ob/ob)) to determine if leptin deficiency overcomes the aphagia of DD mice. DD x Lep(ob/ob) mice became obese when treated daily with L-DOPA, but when L-DOPA treatment was terminated the double mutants were capable of movement, but did not feed. Our data show that dopamine is required for feeding in leptin-null mice.
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When DA-deficient mice are crossed with obese leptin (Ob/Ob)-deficient mice, the lack of DA blocks the increased feeding behavior normally present in the leptin-deficient mice.
“Interestingly, when the DA-deficient mice are crossed with obese leptin (Ob/Ob)-deficient mice, the lack of DA blocked the increased feeding behavior normally present in the leptin (Ob/Ob)-deficient mice [305].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [305]
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- Authors
- Szczypka, M. S., Rainey, M. A., & Palmiter, R. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Palmiter, Richard D.
- ORCID
- Palmiter, Richard D.
- Venue
- Nature Genetics
- Published
- 2000-05
- Volume
- 25
- Issue
- 1
- Pages
- 102-104
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2044399205
- Cited by
- 134
- References
- 25
- Citations by year
- 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 8 · 2012: 8
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 09172, F32HD008121, HD-08121)
- 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
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- dopamine, hyperphagia, leptin deficiency, L-DOPA, feeding behavior, obesity, substantia nigra, ventral tegmental area, nucleus accumbens, lateral hypothalamus, energy balance
- MeSH terms
- Animals, Dopamine, Feeding Behavior, Hyperphagia, Mice, Obese, Leptin, Mice
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