Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO
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Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D 2/3 R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D 2/3 Rs when compared with normal weight (NW) individuals. A D 3-preferring D 2/3 R agonist tracer, [11 C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D 2/3 R availability within striatal reward regions. To date, OB individuals have not been studied with [11 C](+)PHNO. We assessed D 2/3 R availability in striatal and extrastriatal reward regions in 14 OB and 14 age- and gender-matched NW individuals with [11 C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D 2/3 R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D 2/3 R availability in those respective regions. A group-by-brain region interaction effect (F 7, 182=2.08, p=0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D 3-rich regions: the substantia nigra/ventral tegmental area (SN/VTA) (+20%; p=0.02), ventral striatum (VST) (+14%; p<0.01), and pallidum (+11%; p=0.02). BMI was also positively associated with D 2/3 R availability in the SN/VTA (r=0.34, p=0.03), VST (r=0.36, p=0.02), and pallidum (r=0.30, p=0.05) across all subjects. These data suggest that individuals who are obese have higher D 2/3 R availability in brain reward regions densely populated with D 3 Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.
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The reward deficiency model suggests that in obesity, decreased dopamine signalling in the striatum reinforces the rewarding properties of food and disrupts corticostriatal communication between the basal ganglia and the extended reward system.
“The reward deficiency model suggests that in obesity, the presence of decreased dopamine signalling in the striatum reinforces the rewarding properties of food and disrupts corticostriatal communication between the basal ganglia (core reward) and the extended reward system 83, 84.”
From History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity (2019) · cites this paper as [84]
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- Authors
- Gaiser, E. C., Gallezot, J.-D., Worhunsky, P. D., Jastreboff, A. M., Pittman, B., Kantrovitz, L., Angarita, G. A., Cosgrove, K. P., Potenza, M. N., Malison, R. T., Carson, R. E., & Matuskey, D.
- Affiliations
- Yale University (US)
- Corresponding author
- Matuskey, David
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2016-07-04
- Volume
- 41
- Issue
- 13
- Pages
- 3042-3050
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5101552
- OpenAlex
- W2462643901
- Cited by
- 59
- References
- 81
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 2
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Yale University
- National Alliance for Research on Schizophrenia and Depression (M132018)
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health (UL1TR000142, UL1TR001863)
- National Institute of Mental Health (T32MH019961)
- National Institute on Drug Abuse (K24DA017899, K12 DA00167, P20DA027844, DA027844, K02DA031750, R03DA027456, K12DA000167, T32DA022975)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK045735)
- National Center for Advancing Translational Sciences
- Yale Center for Clinical Investigation, Yale School of Medicine
- 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 › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- obesity, dopamine D2/D3 receptors, [11C]-(+)-PHNO, substantia nigra/ventral tegmental area, ventral striatum, globus pallidus, body mass index
- MeSH terms
- Adult, Brain, Female, Humans, Male, Middle Aged, Obesity, Oxazines, Cohort Studies, Body Mass Index, Case-Control Studies, Receptors, Dopamine D2, Dopamine Agonists, Positron-Emission Tomography, Receptors, Dopamine D3, Young Adult
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