Ventral striatum binding of a dopamine D2/3 receptor agonist but not antagonist predicts normal body mass index

Positron emission tomography research has shown that dopamine D2/3 receptor (D2/3R) availability is negatively correlated with body mass index (BMI) in obese but not in healthy subjects. However, previous positron emission tomography studies have not looked specifically at the ventral striatum (VS), which plays an important role in motivation and feeding. Furthermore, these studies have only used antagonist radiotracers. Normal-weight rats given free access to high-fat diets demonstrate behavioral sensitization to D2/3R agonists but not to antagonists. Sensitization is associated with increased D2/3R affinity, which affects binding of agonists but not antagonists.

We examined the association between BMI within the nonobese range (18.6-27.8) and D2/3R availability in the VS with the use of the agonist radiotracer [(11)C]-(+)-PHNO (n = 26) and the antagonist [(11)C]-raclopride (n = 35) in healthy humans.

In the VS, we found a positive correlation between BMI and [(11)C]-(+)-PHNO binding but no relationship with [(11)C]-raclopride binding. Secondary analyses revealed no relationship between BMI and binding in the dorsal striatum with either radiotracer.

We propose that in nonobese individuals, higher BMI may be associated with increased D2R affinity in the VS. This increased affinity may potentiate the incentive salience of food cues and counteract the effects of satiety cues, thereby increasing feeding.