Brain dopamine and obesity.
BACKGROUND
The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain.


METHODS
Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG).


RESULTS
Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery.


CONCLUSIONS
The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.
Wang
G J
GJ
Department of Medicine, Brookhaven National Laboratory, Upton, New York 11973, USA. giwang@bnl.gov
Volkow
N D
ND
Logan
J
J
Pappas
N R
NR
Wong
C T
CT
Zhu
W
W
Netusil
N
N
Fowler
J S
JS
D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D017448:Receptors, Dopamine D2; D005947:Glucose