Alterations of central dopamine receptors before and after gastric bypass surgery

Background: While bariatric surgery has proved highly successful at producing sustained weight loss, variability in treatment response persists. A better understanding of the pathophysiology of appetite and obesity may improve patient selection and management. Research into feeding behavior and satiety has focused on the role of dopamine in reward-based behaviors. Specifically, positron-emission computed tomography (PET) has demonstrated reduced brain dopamine receptor availability in obese subjects compared to controls. This may be due to a primary deficiency in dopamine receptors or to secondary dopamine receptor downregulation. We performed a preliminary study to investigate dopamine D2 receptor activity in obese subjects before and after laparoscopic Roux-en Y gastric bypass (LGBP). Methods: Five female subjects, ages 20 to 38 years old with a mean body mass index of 45, underwent PET with [C-11] raclopride injection. Five regions of interest were studied: ventral striatum, anterior and posterior putamen, and anterior and posterior caudate nucleus. Repeat PET was performed at 6 weeks following LGBP. D2 receptor binding was compared within subjects pre- and post-surgery. Baseline D2 binding was also compared to historical nonobese controls. Results: D2 receptor availability increased 6 weeks after gastric bypass surgery. The increase in receptor availability appeared roughly proportional to the amount of weight lost. No significant difference in D2 binding was seen between the obese subjects and historical nonobese controls. Conclusions: Brain available dopamine D2 binding appears to increase following GBP. This preliminary finding needs to be replicated in a larger population but suggests that diminished D2 binding in the obese may be due to D2 receptor downregulation. Changes in available dopamine receptor binding may play an important role in centrally mediated appetite suppression and resultant weight loss after LGBP.