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

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 D(2/3)Rs when compared with normal weight (NW) individuals. A D-3-preferring D2/3R agonist tracer, [C-11](+) 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 [C-11](+) PHNO. We assessed D2/3R availability in striatal and extrastriatal reward regions in 14 OB and 14 age-and gender-matched NW individuals with [C-11](+) 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 (F-7.82 = 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 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 D(3)Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.