Cited by 59Neurotransmitter Receptor Influence on BehaviorRegulation of Appetite and ObesitySchizophrenia research and treatment

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

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Gaiser, Edward C, Gallezot, Jean-Dominique, Worhunsky, Patrick D, Jastreboff, Ania M, Pittman, Brian, Kantrovitz, Lauren, Angarita, Gustavo A, Cosgrove, Kelly P +4 more·2016·Neuropsychopharmacology

Abstract

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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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
Venue
Neuropsychopharmacology
Published
2016-07-04
Volume
41
Issue
13
Pages
3042-3050
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
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
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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