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Dopamine Synthesis and Receptor Profile Vary as a Function of Body Mass Index in Humans

Friday, September 18, 2015 — Poster Session V

2:00 p.m. – 3:30 p.m.
FAES Terrace

* FARE Award Winner


  • AM Ianni
  • DP Eisenberg
  • CE Hegarty
  • JC Masdeu
  • MD Gregory
  • PD Kohn
  • KF Berman


Obesity is a worldwide epidemic with significant adverse health consequences. Dysfunction of the mesolimbic dopamine system, which mediates the rewarding effects of appetitive stimuli such as food, has been implicated in the development of obesity. Furthermore, striatal D2 receptor levels are decreased in obese individuals and inversely correlated with future weight gain and food seeking-behavior in rats. However, no studies to date have assessed the roles of both dopamine synthesis and receptor density in healthy humans in the normal to obese range. Characterizing the dopaminergic signature related to higher BMI could provide insight into an important neural mechanism underlying the obesity epidemic. Seventy-three healthy volunteers (mean age 36.36, range 18.75-57.90; mean BMI 25.92, range 17.91-35.93; 34 females) completed three PET scans on separate days to assess dopamine presynaptic synthesis capacity (with [18F]DOPA), and D1 and D2 receptor binding potential (with [11C]NNC112 and [18F]Fallypride, respectively). A structural MRI scan was used for registration and definition of regions of interest including the putamen, caudate nucleus, ventral striatum, and midbrain. We found that BMI correlated positively with presynaptic dopamine synthesis capacity in the midbrain (r=0.271, p=0.022) and the left ventral striatum (r=0.300, p=0.011). In addition, BMI correlated negatively with D2 receptor binding potential in the midbrain (r=-0.232, p=0.049) and the caudate nucleus (bilateral: r=-0.239, p=0.046; left: r=-0.272, p=0.022). Taken together, these data suggest that a neural signature related to BMI across the normal to obese range includes an overactive tonic mesolimbic dopamine reward system with impaired regulation by D2 receptors.

Category: Neuroscience