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 D-2 receptors in brain. Methods Brain dopamine D-2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D-2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D-2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[F-18]fluoro-D-glucose (FDG). Findings Striatal dopamine D-2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p less than or equal to0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D-2 receptors (r=0.84; p less than or equal to0.002); the individuals with the lowest D-2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D-2 receptors were not due to a systematic reduction in radiotracer delivery. Interpretation The availability of dopamine D-2 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.