Imaging of Brain Dopamine Pathways: Implications for Understanding Obesity Gene-Jack Wang, MD, Nora D. Volkow, MD, Panayotis K. Thanos, PhD, and Joanna S. Fowler, PhD Medical Department (GJW, JSF), Brookhaven National Laboratory, Upton, NY; Mount Sinai School of Medicine (GJW, JSF), New York, NY; and National Institute of Drug Abuse/National Institute of Alcohol Abuse and Alcoholism (NDV, PKT), Bethesda, MD Abstract Obesity is typically associated with abnormal eating behaviors. Brain imaging studies in humans implicate the involvement of dopamine (DA)-modulated circuits in pathologic eating behavior(s). Food cues increase striatal extracellular DA, providing evidence for the involvement of DA in the nonhedonic motivational properties of food. Food cues also increase metabolism in the orbitofrontal cortex indicating the association of this region with the motivation for food consumption. Similar to drug-addicted subjects, striatal DA D2 receptor availability is reduced in obese subjects, which may predispose obese subjects to seek food as a means to temporarily compensate for understimulated reward circuits. Decreased DA D2 receptors in the obese subjects are also associated with decreased metabolism in prefrontal regions involved in inhibitory control, which may underlie their inability to control food intake. Gastric stimulation in obese subjects activates cortical and limbic regions involved with self-control, motivation, and memory. These brain regions are also activated during drug craving in drug-addicted subjects. Obese subjects have increased metabolism in the somatosensory cortex, which suggests an enhanced sensitivity to the sensory properties of food. The reduction in DA D2 receptors in obese subjects coupled with the enhanced sensitivity to food palatability could make food their most salient reinforcer putting them at risk for compulsive eating and obesity. The results from these studies suggest that multiple but similar brain circuits are disrupted in obesity and drug addiction and suggest that strategies aimed at improving DA function might be beneficial in the treatment and prevention of obesity. Keywords brain dopamine; obesity; positron emission tomography The prevalence of obesity is increasing worldwide, which varies remarkably across ethnic groups and cultures, and across age groups. In the United States, approximately 90 million Americans are obese. Lately, the prevalence of obesity is leveling off in women but is increasing in men, children, and adolescents. 1 Obesity is associated with an increased risk of all-cause morbidity and mortality, which places a sense of urgency to understand the processes that have contributed to this epidemic. Obesity represents the upper end of a bodyweight continuum, rather than a qualitatively different state. Obesity can derive from a variety of causes (ie, genetic, culture, nutrition intake, physical activity). 2 Most notably, obesity is more prevalent (10 times more likely) in persons whose parents, brothers, or sisters are obese. Studies in identical twins have clearly demonstrated that genetics play a Copyright © 2009 American Society of Addiction Medicine Send correspondence and reprint requests to Gene-Jack Wang, MD, Medical Department, Brookhaven National Laboratory, Upton, New York, NY, 11973. gjwang@bnl.gov. NIH Public Access Author Manuscript J Addict Med. Author manuscript; available in PMC 2011 May 20. Published in final edited form as: J Addict Med. 2009 March ; 3(1): 8–18. doi:10.1097/ADM.0b013e31819a86f7. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript