Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation
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A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction and attention deficit hyperactivity disorder. As disruption of D2R signaling in the ventral striatum--including the nucleus accumbens (NAc)--impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that postsynaptic D2R overexpression in the NAc specifically increases an animal's willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc.
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Postsynaptic overexpression in the nucleus accumbens increases in animals the willingness to expend efforts to obtain a goal.
“In contrast, postsynaptic overexpression in the nucleus accumbens increases in animals the willingness to expend efforts to obtain a goal (Trifilieff et al. 2013).”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Trifilieff et al. 2013
Higher dopamine transmission and D2-dependent dopamine signaling in the nucleus accumbens are associated with greater willingness to work for larger but more effortful rewards.
“In other words, higher dopamine transmission and D2-dependent dopamine signaling in the nucleus accumbens are associated with greater willingness to work for larger but more effortful rewards, while lower dopamine and D2 receptor activity shifts animal’s choice towards less effortful and smaller immediate rewards (Figure 2).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Trifilieff et al., 2013
D2 receptor overexpression in the ventral striatum, but not the dorsal striatum, selectively enhances willingness to expend effort to obtain a preferred outcome over a smaller, less effortful reward.
“In addition, we have recently shown that D2 receptor overexpression in the ventral – but not dorsal - striatum selectively enhances willingness to expend effort to obtain a preferred outcome over a smaller, but less effortful reward (Trifilieff et al., 2013).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Trifilieff et al., 2013
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- Authors
- Trifilieff, P., Feng, B., Urizar, E., Winiger, V, Ward, R. D., Taylor, K. M., Martinez, D., Moore, H., Balsam, P. D., Simpson, E. H., & Javitch, J. A.
- Affiliations
- New York State Psychiatric Institute (US)
- Columbia University (US)
- Corresponding author
- Javitch, J A
- Venue
- Molecular Psychiatry
- Published
- 2013-05-28
- Volume
- 18
- Issue
- 9
- Pages
- 1025-1033
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4030518
- OpenAlex
- W2085782088
- Cited by
- 206
- References
- 64
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 7 · 2023: 12 · 2022: 14 · 2021: 14 · 2020: 14 · 2019: 19 · 2018: 20 · 2017: 16 · 2016: 22 · 2015: 23 · 2014: 22 · 2013: 4
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Mental Health (P50MH086404, F32MH090750, MH054137, MH086404, MH068073, R01MH068073, R01MH054137)
- National Institute on Drug Abuse (K05DA022413, DA-022413)
- 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 D2 receptor, nucleus accumbens, dorsal striatum, motivation, viral gene delivery, operant conditioning, effort-based decision making
- MeSH terms
- Analysis of Variance, Animals, Conditioning, Classical, Conditioning, Operant, Gene Expression Regulation, Genetic Vectors, Mice, Inbred C57BL, Microtubule-Associated Proteins, Motivation, Nucleus Accumbens, Reward, Tritium, Receptors, Dopamine D2, Mice, Knockout, Green Fluorescent Proteins, Mice
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