Central dopamine receptors: Radiotracers unveiling the Role of dopaminergic tone in obesity

Brain dopamine type 2 and 3 receptors (D2/3R) have been postulated to play a role in obesity. However, results from molecular neuroimaging studies exploring these receptors in obesity are not consensual. These inconsistencies may be due to the distinct characteristics of radiotracers that confound the interpretation of D2/3R assessment. Only three meta-analyses reported their results across radiotracers. Although all agree that obesity severity influences D2/3R availability, results vary for [¹¹C]raclopride. Further, D2/3R assessment has been commonly interpreted as reflecting receptor density or availability. An alternative interpretation could be related to changes in endogenous central dopaminergic tone. The main question is whether the hypothesis of a quadratic relationship between dopaminergic tone and degree of obesity is suitable for the distinct characteristics of radiotracers. To answer this question and clarify the role of dopaminergic tone in obesity, we systematically reviewed this issue across radiotracers. Out of 514 articles, 15 articles were selected for review. Besides obesity severity, this study highlights the influence of radiotracer characteristics when assessing D2/3R. The tested hypothesis proved to be more suitable for radiotracers more susceptible to endogenous dopamine or with a lower affinity to D2/3R, supporting the quadratic relationship between dopaminergic tone and degree of obesity. While the role of D2/3R density in obesity may be relevant, dopaminergic tone seems to have a greater impact on the obesity-related differences found in these receptors. Finally, neuropsychological factors should be tested in addition to body mass index, as they may better reflect altered brain dopaminergic function.