Dopamine Signaling in the Dorsal Striatum Is Essential for Motivated Behaviors: Lessons from Dopamine‐Deficient Mice
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Genetically engineered mice that lack tyrosine hydroxylase in all dopaminergic neurons become hypoactive and aphagic, and they starve by 4 weeks of age. However, they can be rescued by daily treatment with l-dopa, which restores activity and feeding for about 10 hours. Thus, these mice can be examined in both dopamine-depleted and dopamine-replete states. A series of behavioral experiments lead to the primary conclusion that in the dopamine-depleted state these mice are not motivated to engage in goal-directed behaviors. Nevertheless, they still have a preference for sucrose, they can learn the location of food rewards, and they can form a conditioned-place preference for drugs. Dopamine signaling can be restored to the striatum by several different viral gene-therapy procedures. Restoring dopamine signaling selectively to the dorsal striatum is sufficient to allow feeding, locomotion, and reward-based learning. The rescued mice appear to have normal motivation to engage in all goal-directed behaviors that have been tested. The results suggest that dopamine facilitates the output from dorsal striatum, which provides a permissive signal allowing feeding and other goal-directed behaviors.
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Dopamine depletion impairs operant responding in reinforcement schedules with high work requirements.
“Moreover, increases in dopamine release facilitate operant responding, whereas dopamine depletion impairs operant responding in reinforcement schedules with high work requirements (Palmiter, 2008; Salamone et al., 2007).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Palmiter, 2008
Increases in dopamine release facilitate operant responding.
“Moreover, increases in dopamine release facilitate operant responding, whereas dopamine depletion impairs operant responding in reinforcement schedules with high work requirements (Palmiter, 2008; Salamone et al., 2007).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Palmiter, 2008
DA-deficient mice die of starvation likely due to decreased motivation to consume food, and replenishing dorsal striatum DA restores feeding and rescues them.
“Indeed, DA-deficient mice die of starvation, likely as a result of a decreased motivation to consume the food, and replenishing the dorsal striatum with DA restores feeding and rescues them (28).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [28]
Rodent experiments show DA signaling through D1 and D2 receptors in dorsal striatum is necessary for feeding and eating-related behaviors.
“Experiments in rodents have shown, for example, that DA signals through both D1 receptors and D2 receptors (D2R) in the dorsal striatum are necessary for feeding and other eating-related behaviors (28).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [28]
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References 70 · Cited by 375
- Authors
- Palmiter, R. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Palmiter, Richard D.
- ORCID
- Palmiter, Richard D.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2008-05
- Volume
- 1129
- Issue
- 1
- Pages
- 35-46
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC2720267
- OpenAlex
- W2074370892
- Cited by
- 375
- References
- 70
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 15 · 2023: 25 · 2022: 24 · 2021: 15 · 2020: 27 · 2019: 20 · 2018: 24 · 2017: 26 · 2016: 31 · 2015: 18 · 2014: 16 · 2013: 26 · 2012: 17
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine signaling, dorsal striatum, dopamine depletion, goal-directed behavior, motivation, feeding behavior, sucrose preference, reward learning, conditioned place preference, viral gene therapy, dopamine replacement therapy, L-DOPA, striatal output
- MeSH terms
- Animals, Behavior, Animal, Dopamine, Feeding Behavior, Motivation, Signal Transduction, Neostriatum, Mice
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