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Pleasure, addiction molecule linked to obesity
By Adam Marcus
Researchers at Brookhaven National Laboratory say they've found that obese people have a thin supply of dopamine receptors, the docking sites on nerve cells that trigger sensations of satisfaction and pleasure. The discovery, which appears in the latest issue of The Lancet, suggests that drugs to stimulate dopamine receptors might break the pattern of unhealthy, addictive eating.
However, one dopamine expert cautions that tinkering with dopamine to shed pounds has proven harder and more treacherous than expected, largely because the dopamine system is easily prone to addiction and habituation.
Dopamine is a brain chemical involved in appetites and drives, as well as motor control, cognition and other functions. The most familiar dopamine-related disorder is Parkinson's disease, which results from the gradual destruction of the factories that produce the messenger molecule.
Earlier research by the Brookhaven group has shown that drug addicts have higher circulating levels of dopamine in their brains -- and fewer receptors for the molecule -- than people who don't take drugs.
In the latest work, the scientists tried to test whether people who chronically overeat have a similar relationship with food as addicts do with drugs: indulging the habit triggers the biochemical pathways of reward.
Dr. Gene-Jack Wang and his colleagues used positron emission tomography (PET) to map the dopamine receptors in 10 severely obese people and 10 control subjects with healthy waistlines.
Fewer receptors found
As a group, the obese men and women had fewer dopamine receptors available to soak up the chemical, particularly sites called D2 receptors, than did their slim counterparts. And the number of D2 receptors dropped with increasing body mass index, a measure of weight to height.
The work is "the first time that anyone has documented that there are brain abnormalities, a biochemical dysfunction, that is likely to be contributing to the pathological behavior" of binge eating, says Dr. Nora Volkow, a co-author of the study.
"We're not saying that these people are obese because they have low D2 receptors. What we're saying is that the low level [of the receptors] contributes to the compulsive administration" of food. Other factors, from hormone trouble to psychological factors, play a role in some cases of obesity, she says.
Serious overeaters may alter their brain chemistry over time to promote the abnormal dopamine activity, Volkow says. "The brain adapts itself, it resets itself. We cannot rule out the possibility that the chronic stimulus of food intake creates a vicious cycle" that shuts down receptors and primes the pleasure-seeking impulse, leading to more eating.
Or, the researchers argue, people with few dopamine receptors may be predisposed to compulsive behaviors, including overeating -- an explanation supported by evidence showing that binge eaters often have relatives with substance abuse problems.
While the latest findings reveal an interesting correlation, Dr. Richard Wurtman, a dopamine expert at the Massachusetts Institute of Technology, says it's probably only that. "It is very, very unlikely to constitute a therapeutic lead," says Wurtman.
Early obesity drugs relied on amphetamines to spur weight loss by provoking dopamine neurons. But they did so at a big price: Amphetamines are addictive and they lead to tolerance, which forces people to take increasing amounts of them to see their effect.
What's more, Wurtman says, "there is no evidence that dopamine itself is involved in food intake," though another brain chemical, serotonin, appears to be.
Even so, Volkow says it may be possible to design a drug that can right the imbalance in dopamine receptors rather than act on dopamine itself. Gene therapy may also be an option, she says. In fact, Volkow says she and her colleagues have already shown that they can block drug-seeking behavior rats by injecting the animals with a virus programmed to make dopamine receptors.
What To Do
Nearly one in five Americans is obese, a condition that puts them at risk of heart disease, diabetes, strokes and many other serious health problems.
Although drug companies are looking for, and would love to find, that magic little weight-loss pill, diet experts say there's only one sure-fire way to lose weight and keep it off: Eat less and exercise.
For more on how to eat right, visit the American Dietetic Association.
To learn more about overweight, try the National Heart, Lung, and Blood Institute or the American Heart Association.