Elevated Dopamine D_2/3 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 (D_2/3R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D_2/3Rs when compared with normal weight (NW) individuals. A D₃-preferring D_2/3R agonist tracer, [¹¹C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D_2/3R availability within striatal reward regions. To date, OB individuals have not been studied with [¹¹C](+)PHNO. We assessed D_2/3R 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 D_2/3R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D_2/3R 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 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 D_2/3R 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 D_2/3R availability in brain reward regions densely populated with D₃Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.