Ventral striatum binding of a dopamine D_2/3 receptor agonist but not antagonist predicts normal body mass index

Background Positron emission tomography research has shown that dopamine D_2/3 receptor (D_2/3R) 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 D_2/3R agonists but not to antagonists. Sensitization is associated with increased D_2/3R affinity, which affects binding of agonists but not antagonists.

Methods We examined the association between BMI within the nonobese range (18.6-27.8) and D_2/3R availability in the VS with the use of the agonist radiotracer [¹¹C]-(+)-PHNO (n = 26) and the antagonist [¹¹C]-raclopride (n = 35) in healthy humans.

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

Conclusions 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.