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Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers

Darcey, V. L.; Guo, J.; Chi, M.; Chung, S. T.; Courville, A. B.; Gallagher, I.; Herscovitch, P.; Howard, R.; La Noire, M.; Milley, L.; Schick, A.; Stagliano, M.; Turner, S.; Urbanski, N.; Yang, S.; Yim, E.; Zhai, N.; Zhou, M. S.; Hall, K. D.

2023-09-28 neurology
10.1101/2023.09.27.23296169 medRxiv
Show abstract

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [18F]fallypride and [11C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m2). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [11C]raclopride (r= -0.51; p<0.0001) but not [18F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [18F]fallypride has greater binding affinity to dopamine type-2 receptors than [11C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.

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