title: Elevated Dopamine D2/3Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO.
abstract: 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.
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.|Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Gaiser
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
authors.forename: Jean-Dominique
authors.identifier: 0000-0003-0399-8374
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.|Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Worhunsky
authors.affiliation: Department of Internal Medicine, Endocrinology, Yale University, New Haven, CT, USA.|Department of Pediatrics, Pediatric Endocrinology, Yale University, New Haven, CT, USA.
authors.forename: Ania M
authors.initials: AM
authors.lastname: Jastreboff
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Kantrovitz
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Angarita
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.|Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.|CASAColumbia and Departments of Neuroscience and Child Study Center, Yale University, New Haven, CT, USA.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Malison
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.|Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Matuskey
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D016022:Case-Control Studies; D015331:Cohort Studies; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000000981:diagnostic imaging*; D010078:Oxazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D018491:Dopamine Agonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide