A comparison of D2 receptor specific binding in obese and normal-weight individuals using PET with (N-[(11)C]methyl)benperidol.

Previous PET imaging studies have demonstrated mixed findings regarding dopamine D2/D3 receptor availability in obese relative to nonobese humans. Nonspecific D2/D3 radioligands do not allow for separate estimation of D2 receptor (D2R) and D3 receptor (D3R) subtypes of the D2 receptor family, which may play different roles in behavior and are distributed differently throughout the brain. These radioligands are also displaceable by endogenous dopamine, confounding interpretation of differences in receptor availability with differing levels of dopamine release. The present study used PET imaging with the D2R-selective radioligand (N-[(11)C] methyl)benperidol ([(11)C]NMB), which is nondisplaceable by endogenous dopamine, to estimate D2R specific binding (BPND) and its relationship to body mass index (BMI) and age in 15 normal-weight (mean BMI = 22.6 kg/m(2)) and 15 obese (mean BMI = 40.3 kg/m(2)) men and women. Subjects with illnesses or taking medications that interfere with dopamine signaling were excluded. Striatal D2R BPND was calculated using the Logan graphical method with cerebellum as a reference region. D2R BPND estimates were higher in putamen and caudate relative to nucleus accumbens, but did not differ between normal-weight and obese groups. BMI values did not correlate with D2R BPND . Age was negatively correlated with putamen D2R BPND in both groups. These results suggest that altered D2R specific binding is not involved in the pathogenesis of obesity per se and underscore the need for additional studies evaluating the relationship between D3R, dopamine reuptake, or endogenous dopamine release and human obesity.

Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity.

Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic ß-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for ß-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower ß-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or ß-cell function in either group. Our findings indicate that individual differences in percent body fat, ß-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including ß-cell function, interact to affect reward discounting in humans.

Emotional Eating Phenotype is Associated with Central Dopamine D2 Receptor Binding Independent of Body Mass Index.

PET studies have provided mixed evidence regarding central D2/D3 dopamine receptor binding and its relationship with obesity as measured by body mass index (BMI). Other aspects of obesity may be more tightly coupled to the dopaminergic system. We characterized obesity-associated behaviors and determined if these related to central D2 receptor (D2R) specific binding independent of BMI. Twenty-two obese and 17 normal-weight participants completed eating- and reward-related questionnaires and underwent PET scans using the D2R-selective and nondisplaceable radioligand (N-[(11)C]methyl)benperidol. Questionnaires were grouped by domain (eating related to emotion, eating related to reward, non-eating behavior motivated by reward or sensitivity to punishment). Normalized, summed scores for each domain were compared between obese and normal-weight groups and correlated with striatal and midbrain D2R binding. Compared to normal-weight individuals, the obese group self-reported higher rates of eating related to both emotion and reward (p<0.001), greater sensitivity to punishment (p=0.06), and lower non-food reward behavior (p<0.01). Across normal-weight and obese participants, self-reported emotional eating and non-food reward behavior positively correlated with striatal (p<0.05) and midbrain (p<0.05) D2R binding, respectively. In conclusion, an emotional eating phenotype may reflect altered central D2R function better than other commonly used obesity-related measures such as BMI.