Dopamine Receptors Implicated in Obesity

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A deficiency of dopamine in the brain may explain why some individuals engage in pathological overeating, resulting in severe obesity, according to a study published in this week's Lancet. Dopamine is a neurotransmitter that acts in the brain and helps regulate feelings of pleasure and modulates the rewarding properties of food.

Based on their findings, the researchers believe that individuals deficient in dopamine receptors may need to eat more than people with higher dopamine levels to induce feelings of satisfaction and gratification.

"There is an interesting correlation with the findings of this study and drug addiction. Dopamine receptor deficiency also has been documented in individuals addicted to various types of drugs including cocaine, alcohol, and opiates. This would suggest that a reduction in dopamine receptors is associated with addictive behavior regardless of whether it is addiction to food or to drugs," said Dr. Alan I. Leshner, director, National Institute on Drug Abuse.

It has been observed previously that in humans drugs such as certain anti-psychotic medications that block dopamine receptors increase appetite and result in significant weight gain, whereas drugs such as methamphetamine that increase brain dopamine levels diminish appetite. However, prior to this study, the role of brain dopamine receptors in human obesity had not been directly evaluated.

Dr. Gene-Jack Wang from Brookhaven National Laboratory, head of the team of researchers who conducted the study, says that the findings from this study "suggest that developing a way to improve dopamine receptor function might lead to better treatment of obesity." A practical treatment for obesity using this approach is not yet possible because there are currently no clinically appropriate dopamine-based drugs that can be used to suppress appetite.

Dr. Wang says, "Currently, the most appropriate practical application of this finding is to urge overweight individuals to exercise. In laboratory animals, exercise has been shown to increase dopamine release and to increase the number of dopamine receptors, which would help quell the urge to pathologically overeat."

In the study, ten severely obese individuals (weight range: 275-390 pounds) were compared with 10 control subjects (weight range: 121-198 pounds). The body mass index (BMI: weight in kilograms divided by the square of height in meters) was ascertained for each individual. The BMI in the obese group averaged about 51.2 and in the control group about 24.7.

In both groups, dopamine receptors in the brain were measured with positron emission tomography (PET) scans and other tests. It was found that dopamine receptor availability was significantly lower in obese than in control individuals. An additional finding was that BMI correlated negatively with the measures of dopamine receptors. Individuals with the lowest dopamine receptor values had the largest BMI.

Dr. Wang cautions that this study "can not determine if the brain changes in the obese individuals are a consequence or cause of obesity." He says additional research is needed to evaluate dopamine receptor levels before and after successful weight loss. "This," he says, "might help determine if the low levels of dopamine receptors are due to changes resulting from large BMI or if they are independent of BMI."