Dopamine and Obesity

Overeating, drug abuse, and the D2 receptor.

A genetic variation in the dopamine D2 receptor predisposes women toward obesity, according to a small but potentially significant study published in the October 17 issue of Science.

While numerous twins studies demonstrate the likelihood of biological factors in obesity, there are few rigorous studies that back up the contention. Now researchers from Yale University and the University of Texas have used brain scans to show that a dopamine-rich structure called the dorsal striatum exhibits “reduced D2 receptor density and compromised signaling” in obese individuals.

Why would this matter? The dorsal striatum releases dopamine in response to the consumption of tasty food. Going right to the sugary heart of the tasty food cornucopia, the researchers used chocolate milkshakes. Women volunteers underwent MRI scans while researchers administered either squirts of milkshake or squirts of a tasteless liquid. The lower the dopamine response to the milkshake in the dorsal striatum, the more likely the woman was to gain weight over the following year. Reduced dopamine receptor density in the dorsal striatum “may prompt them to overeat in an effort to compensate for this reward deficit,” the study authors concluded. The all-female study lends more evidence to the notion that dopamine D2 variations “are associated with both obesity and substance abuse....”

Dr. Nora Volkow, director of the National Institute on Drug Abuse (NIDA), told Associated Press: “It takes the gene associated with greater vulnerability for obesity and asks the question why. What is it doing to the way the brain is functioning that would make a person more vulnerable to compulsively eat food and become obese?”

Historically, however, the D2 allele has been a controversial locus of research in addiction medicine. In 1990, a research team reported in the Journal of the American Medical Association that the A-1 allele controlling production of the dopamine D2 receptor was three times as common in the brains of deceased alcoholics. The aberrant form of the gene was found in 77 per cent of the alcoholics, compared with only 28 per cent of the non-alcoholics. But attempts to replicate the research did not meet with much success. (See Bower, Bruce. “Gene in the Bottle.” Science News, September 21, 1991. p.19). In addition, the findings from the nationwide Collaborative Study on the Genetics of Alcoholism were not supportive of the D2 hypothesis. (“We believe it doesn’t increase the risk for anything,” one researcher said bluntly.) Well-known researcher Robert Cloninger weighed in with a paper demonstrating that when you broadened the samples and took another look, the D2 connection faded away, suggesting that the D2 allele in question may play a second-order role of some sort. (See Holden, Constance. “A Cautionary Genetic Tale: The Sobering Story of D2.” Science. June 17, 1994. 264 p.1696 ).

The current Science study concludes that “individuals who show blunted striatal activation during food intake are at risk for obesity.... behavioral or pharmacologic interventions that remedy striatal hypofunctioning may assist in the prevent and treatment of this pernicioujs health problem.” NIDA’s Volkow, quoted in the Washington Post, said: “Dieting is a complex process and people don’t like it. Physical activity, which also activates the dopamine pathway, may be a mechanism for reducing the compulsive activity of overeating.”

Dr. Eric Stice of the Oregon Research Institute, the lead scientist on the study, told AP that the findings might have implications for parents. Since most parents don’t know if they possess the suspect variation, Stice suggested than parents could start attending more to the diets of children, “and not get their brains used to having crappy food.”


Photo Credit: Cell Science

dopamine

Food Addiction and Dopamine

Why your brain likes sweets.

The brain's ability to sniff out calories in the form of sugar depends upon sugar's drug-like effect on the dopamine-rich reward center known as the nucleus accumbens, according to a study published in the March 27 issue of Neuron. This tiny structure in the mid-brain is also the locus of reward activity for all addictive drugs.

In the study, Ivan de Araujo and colleagues at Duke University and the Universidade do Porto in Portugal demonstrated that lab mice lacking the ability to taste sweet foods still preferred sugary water to regular water. The genetically altered mice, lacking functional taste receptor cells for bitter and sweet, consistently chose to consume sugar water--even though they could not sense the sugar. (The lab animals were also prevented from smelling or sensing textural differences in the offerings.)

"Our findings suggest that calorie-rich nutrients can directly influence brain reward circuits that control food intake independently of palatability or functional taste transduction," the researchers wrote.

The findings offer new clues to obesity, and also bolster the contention that simple carbohydrate foods--because of their effect on reward pathways in the brain--can be addictive for certain people. As Tamas Horvath of Yale University's School of Medicine told Science News (sub. required): "This is a very exciting new element in how you get addicted to food. It doesn't even matter how it tastes."

In the same article, written by Amy Maxmen, study author de Araujo said: "The animal's reward processing systems were sensitive to changes in metabolism, not just flavor. This is a new system."

The "sweet-blind" animals did not go for the low-cal alternative, when they were offered water mixed with sucralose, otherwise known as Splenda. Low-cal sweeteners did not result in a similar dopamine boost along the reward pathways of the brain.

The brain's ability to "sense" calories may help explain why diet foods are often ignored in favor of sweets. As Ewan Callaway of New Scientist put it, "Anyone who has devoured a tub of ice cream in one sitting knows that delicious foods can override our body's pleas of 'enough.'" We have increased levels of dopamine in the nucleus accumbens to thank for that.

As De Araujo explained to New Scientist, "even when you do not stimulate the sensory pathways in the mouth you still have this reward signal in the brain."

In a preview of the article in the same issue of Neuron, Zane Andrews and Tamas Horvath speculate that "high-fructose corn syrup is an ubiquitous sweetener in American society.... It may be that fructose produces stronger activation of the reward system and that removing high-fructose corn syrup as a sweetener will curb some desire for these products."

Photo Credit: Biz/Ed

dopamine addiction

Food Addiction

Carbohydrates on the Brain, Food Rehab in the Future

Earlier this month, Yale University hosted the first-ever conference on Food and Addiction. Dr. Nora Volkow of the National Institute on Drug Abuse told the collection of experts on nutrition, obesity and drug addiction that “commonalities in the brain’s reward mechanisms” linked compulsive eating with addictive drug use. “Impaired function of the brain dopamine system could make some people more vulnerable to compulsive eating,” Volkow said.

Moreover, animal studies and brain imaging research in humans strongly support the notion of food addiction. In particular, research has pointed toward a form of food addiction known as “carbohydrate-craving obesity.” Dr. Mark Gold, chief of addiction studies at the McKnight Institute at the University of Florida, and a well-known authority on cocaine abuse, argued that “failed diets and attempts to control overeating, preoccupation with food and eating, shame, anger, and guilt look like traditional addictions.”

Conference organizer Kelly Brownell, director of the Rudd Center for Food Policy and Obesity at Yale, conceded that “it wasn’t obesity experts who got interested in addiction, it was the addiction scientists who got interested in food.” Brownell suggested that psychologists have been slower to grasp the import of food addiction “in part because of a bias that obesity is all about failure and personal responsibility, so why look at biology?”

As Dr. Gold summed it up, “It turns out that food and drugs compete for the same reward system in the brain.”

SOURCES:

--“Yale Hosts Historic Conference on Food and Addiction.” Yale University Office of Public Affairs. July 9, 2007. http://www.yale.edu/opa/newsr/07-07-09-01.all.html

--Hellmich, Nancy. “Does food ‘addiction’ explain explosion of obesity?” USA Today, July 9, 2007.

--“Yale Hosts Historic Conference on Food Addiction.” Medical News Today. 11 July 2007. www.medicalnewstoday.com

--Hathaway, William. “Experts Chew Over Eating as Addiction.” The Hartford Courant. July 11, 2007. http://www.courant.com/news/health