Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic

Zhou, Qun-Yong; Palmiter, Richard D.

doi:10.1016/0092-8674(95)90145-0

Cited by 731Neurotransmitter Receptor Influence on BehaviorParkinson's Disease Mechanisms and TreatmentsNeuroscience and Neuropharmacology Research

Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic

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Zhou, Qun-Yong, Palmiter, Richard D.·1995·Cell

DOI 10.1016/0092-8674(95)90145-0

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Abstract

Mice unable to synthesize dopamine (DA) specifically in dopaminergic neurons were created by inactivating the tyrosine hydroxylase (TH) gene then by restoring TH function in noradrenergic cells. These DA-deficient (DA-/-) mice were born at expected frequency but became hypoactive and stopped feeding a few weeks after birth. Midbrain dopaminergic neurons, their projections, and most characteristics of their target neurons in the striatum appeared normal. Within a few minutes of being injected with L-dihdroxyphenylalanine (L-DOPA), the product of TH, the DA-/- mice became more active and consumed more food than control mice. With continued administration of L-DOPA, nearly normal growth was achieved. These studies indicate that DA is essential for movement and feeding, but is not required for the development of neural circuits that control these behaviors.

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DA-deficient mice cannot make DA, are born normal but fail to thrive, have decreased food intake, gradually become hypoactive and hypophagic, and die at 3 weeks of age.
“These DA-deficient mice cannot make DA, and are born normal but fail to thrive, have decreased food intake, gradually become hypoactive and hypophagic, and die at 3 weeks of age [301].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [301]
DA release in the striatum is required to integrate relevant signals for sustained feeding.
“These results suggest that DA release in the striatum is required to integrate relevant signals for sustained feeding [301,314,315].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [301]
Without dopamine, hungry mice are hypoactive and starve to death, even though food and water are readily available.
“Without dopamine, hungry mice are hypoactive and starve to death, even though food and water are readily available, literally in front of their noses.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Zhou and Palmiter, 1995

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Authors: Zhou, Q.-Y., & Palmiter, R. D.
Affiliations: Howard Hughes Medical Institute (US)
ORCID: Palmiter, Richard D.
Venue: Cell
Publisher: Elsevier BV
Published: 1995-12
Volume: 83
Issue: 7
Pages: 1197-1209
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(95)90145-0
OpenAlex: W1971764800
Cited by: 731
References: 78
Citations by year: 2026: 13 · 2025: 18 · 2024: 7 · 2023: 13 · 2022: 25 · 2021: 22 · 2020: 18 · 2019: 22 · 2018: 30 · 2017: 29 · 2016: 29 · 2015: 24 · 2014: 28 · 2013: 29 · 2012: 29
FWCI: 4.13
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6438 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 09172)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: dopamine deficiency, tyrosine hydroxylase, dopaminergic neurons, hypoactivity, anorexia, feeding behavior, locomotor activity, L-DOPA, striatum, knockout mice, neural circuit development
MeSH terms: Adrenergic Fibers, Animals, Animals, Newborn, Behavior, Animal, Dopamine, Dopamine beta-Hydroxylase, Drinking Behavior, Dynorphins, Embryo, Mammalian, Feeding Behavior, Immunohistochemistry, Levodopa, Mesencephalon, Mice, Transgenic, Mutation, Neurons, Norepinephrine, Substance P, Tyrosine 3-Monooxygenase, Neostriatum, In Situ Hybridization, Transgenes, Mice

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Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic

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