Obesity is a major public health problem second only to tobacco smoking. This coupled with the increase in the number of obese individuals places a sense of urgency on understanding the mechanisms underlying pathological overeating so that effective treatments can be developed. In a recent study we documented low dopamine D2 receptor availability in pathologically obese subjects (BMI > 40 kg/m2), using positron emission tomography (PET) and the radioligand [11C]raclopride. Obese subjects also had higher rates of glucose metabolism in dopamine projection areas than the control subjects. These studies plus the known involvement of the dopamine system in reward and reinforcement have led us to postulate that low brain dopamine activity in obese subjects predisposes them to excessive use of food. This notion is supported by reports of low D2 receptors in individuals dependent on alcohol, cocaine or opiates. However, another potential explanation is that the low D2 receptor density is a cause rather than a predisposing factor of obesity. Here we propose to replicate this study in spontaneously obese bonnet macaques (Macaca radiata) available at the SUNY-Downstate Medical Center. In addition to D2 receptor studies, we will assess the dopamine transporter status of the obese and lean macaques, using [11C]d-threomethylphenidate. This strategy will allow both presynaptic and postsynaptic measures of the dopamine system. Our major purpose is to conduct the preliminary work necessary for studies in these macaques in which the causal relationship between obesity and low D2 receptor status can be evaluated in a controlled manner. In particular, this would allow us to address the hypothesis that weight reduction is associated with increases in D2 receptor levels to the normal range
| Wang, Gene-Jack; Geliebter, Allan; Volkow, Nora D et al. (2011) Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring) 19:1601-8 |
| Wang, Gene-Jack; Volkow, Nora D; Thanos, Panayotis K et al. (2009) Imaging of brain dopamine pathways: implications for understanding obesity. J Addict Med 3:8-18 |
