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Neuropsychopharmacology. 2016 Dec;41(13):3042-3050. doi: 10.1038/npp.2016.115. Epub 2016 Jul 4.

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

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  • 1Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
  • 2Department of Psychiatry, Yale University, New Haven, CT, USA.
  • 3Department of Internal Medicine, Endocrinology, Yale University, New Haven, CT, USA.
  • 4Department of Pediatrics, Pediatric Endocrinology, Yale University, New Haven, CT, USA.
  • 5CASAColumbia and Departments of Neuroscience and Child Study Center, Yale University, New Haven, CT, USA.


Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D2/3R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D2/3Rs when compared with normal weight (NW) individuals. A D3-preferring D2/3R agonist tracer, [11C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D2/3R availability within striatal reward regions. To date, OB individuals have not been studied with [11C](+)PHNO. We assessed D2/3R availability in striatal and extrastriatal reward regions in 14 OB and 14 age- and gender-matched NW individuals with [11C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D2/3R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D2/3R availability in those respective regions. A group-by-brain region interaction effect (F7, 182=2.08, p=0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D3-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 D2/3R 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 D2/3R availability in brain reward regions densely populated with D3Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.

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