This study replicates earlier findings that obese subjects have lower striatal D2/3R availability than non-obese subjects. The first two studies to demonstrate this difference [7, 8] were in a largely overlapping sample of obese subjects with a mean BMI of 51 kg/m2. Haltia et al.  replicated this finding only with a voxel-based analysis, reporting a lower D2/3R availability in obese subjects in a cluster partly covering the striatum. The major difference with the first study was that the average BMI of the obese group was lower (33 kg/m2). In the present study, we included obese women with a mean BMI of 47 kg/m2, and we were able to replicate the finding with a ROI analysis. Thus, this suggests a decrease in striatal D2/3R availability with increasing BMI. This is strengthened by the finding of a negative correlation between the BMI and striatal D2/3R availability in the obese groups in the previous studies [7, 9].
It should be mentioned that one study, performed in patients undergoing bariatric surgery, found no significant difference in striatal D2/3R availability between obese subjects and historical controls . However, this study included only five women per group. Although no statistical test was described, absolute D2/3R availability shown in a graph was lower in the obese than in control subjects. Thus, this study may not have been able to detect a difference in D2/3R availability between obese and controls due to insufficient sample size.
The present study nor the previous ones can solve the question whether lower striatal D2/3R availability in obesity is a causal factor in obesity or rather the result of the obese condition. Carriers of the Taq1A allele in the gene encoding for the D2/3R show a decreased D2/3R expression  and have a higher susceptibility for obesity . This would suggest that lower D2/3R expression levels are a pre-existing condition that plays a role in the susceptibility. However, in rats, it has been shown that downregulation of striatal D2/3R can be induced by a cafeteria diet and that this is associated with an increase in the susceptibility for reward deficits and compulsive eating behaviour . The available studies on effects of weight loss after bariatric surgery on D2/3R availability are scarce and show conflicting results [15, 17].
The involvement of dopamine signalling in the regulation of food intake has been clearly established . Its major functions are related to motivation and reward and involvement in salience attribution to food. Food intake induces a dopamine release in the striatum thereby exerting its rewarding effect . This is similar to the effects of drug abuse , suggesting parallels between obesity and drug addiction . Part of the aetiology of both conditions could be explained by a hypodopaminergic mesolimbic system that leads to increased motivation for food and drugs, respectively . In this context, it is of interest that the extent of lower striatal D2/3R availability in obese subjects is comparable to cocaine and alcohol abusers . Nevertheless, lower striatal D2/3R availability is probably only one underlying mechanism in the disturbed balance between energy intake and energy expenditure present in obese subjects. Peripheral metabolic signals, e.g. leptin, ghrelin, insulin and hypothalamic neuropeptides are able to interact with the striatal dopaminergic system as well . This complexity may explain the considerable overlap in striatal D2/3R availability between obese and non-obese women in the present study.
A limitation of this study is the difference in age between the obese and control subjects. To correct this, age was added as a co-variate to the statistical model. Besides, it has previously been shown that age leads to a decrease of 4.6% to 8.2% D2/3R availability per decade [14, 20]. As we found a 23% lower D2/3R availability in our obese subjects, this difference is too large to be explained by age per se. Therefore, we believe that the age difference does not significantly affect our results and conclusions.
The two groups were not scanned under the same conditions regarding fasting state. While the obese patients were scanned after an overnight fast, the healthy controls were not scanned in the fasted state. As previously mentioned, food intake induces a striatal dopamine release , so this can transiently lead to increased dopamine levels. However, even if the fed state in the lean group would have led to increased dopamine levels, this would have resulted in a decrease of D2/3R availability and subsequently in an underestimation of the presently observed difference between the obese and lean groups.
Unlike previous studies on D2/3R availability in obesity with mixed gender samples, this study only included women. Although this may affect the extrapolation of the results to men, it increased the homogeneity of the subjects and demonstrated that the lower D2/3R availability is also detectable in females only.