US researchers working with rats have shown for the first time that the compulsion to overeat that leads to obesity has the same biological mechanism as seen in addiction to drugs like cocaine and heroin abuse: it affects the brain’s pleasure circuitry in a similar way.

You can read about the study, conducted by Scripps Research Associate Professor Paul J Kenny and graduate student Paul M Johnson from The Scripps Research Institute in Jupiter, Florida, in the 28 March advanced online issue of Nature Neuroscience.

According to a press statement from The Scripps Research Institute on Sunday, the study appears to confirm what many obesity patients have been saying for years: like drug addiction, binging on junk food is very hard to stop.

Kenny and Johnson show that as pleasure centers in the brain become less responsive, rats quickly develop compulsive overeating habits, eating increasing amounts of high-calorie, high-fat foods until they become obese.

This is the same progressively deteriorating chemical balance in reward brain circuits seen in rats that overconsume cocaine or heroin that is thought to lie behind the development of compulsive drug use.

Kenny told the press that the study confirms that junk food can become “addictive”. It explains what happens in the brains of the animals when they can easily get hold of high-calorie, high-fat food, he said.

“It presents the most thorough and compelling evidence that drug addiction and obesity are based on the same underlying neurobiological mechanisms,” added Kenny, explaining that:

“In the study, the animals completely lost control over their eating behavior, the primary hallmark of addiction.”

One of the tests of addictive behaviour is to train lab animals to anticipate an electric shock. At first the animals receive the mild shocks at the same time as a light coming on, eventually they learn to anticipate the shock when they see the light and they avoid doing the thing that then triggers the shock.

In this case, the rats that had become “addicted” to junk food ignored the light and continued to binge, highlighting how motivated they were, said Kenny.

For the junk food they used in the study, Kenny and Johnson bought foods people love to eat: cheesecake, bacon, sausage, Ding-Dongs (a flat-shaped chocolate cake popular in the US).

“The stuff that you enjoy, but you really shouldn’t eat too often,” Kenny said, as reported by Reuters.

They also bought healthy foods and put the rats into three groups: (1) a balanced healthy diet group, (2) a healthy diet group with access to high-calorie “junk” food for one hour a day, and (3) a group that was fed healthy food but also had unlimited access to the high-calorie “junk” food.

Kenny said the third group quickly showed a preference for the junk food, ate it all day long and quickly became obese.

“They always went for the worst types of food,” said Kenny.

“As a result, they took in twice the calories as the control rats,” he added, explaining that when they removed the junk food and tried to feed them a healthy diet, “the salad bar option”, they just refused to eat.

“The change in their diet preference was so great that they basically starved themselves for two weeks after they were cut off from junk food,” said Kenny.

“It was the animals that showed the “crash” in brain reward circuitries that had the most profound shift in food preference to the palatable, unhealthy diet. These same rats were also those that kept on eating even when they anticipated being shocked,” he added.

What happens in addiction is “lethally simple”, said Kenny, “the body adapts remarkably well to change — and that’s the problem”.

“When the animal overstimulates its brain pleasure centers with highly palatable food, the systems adapt by decreasing their activity. However, now the animal requires constant stimulation from palatable food to avoid entering a persistent state of negative reward,” he explained.

After this first stage, where they showed the obese rats had developed clear addiction-like food seeking behavior, Kenny and Johnson then examined the underlying biological mechanisms that might explain the change.

They were particularly interested in the dopamine D2 receptor in the brain, a receptor that is already known to play a role in vulnerability to drug addiction and obesity. The receptor responds to dopamine, a chemical that the brain releases in response to pleasurable experiences like food, drugs and sex.

For example, in cocaine abuse, the drug blocks the retrieval of dopamine, causing it to flood the brain and overstimulate the receptors. Eventually this leads to physical changes in the brain and how it responds to the drug.

Kenny and Johnson have shown this to be the same in addiction to junk food.

Kenny said their findings confirm what they and many others had long suspected:

“Overconsumption of highly pleasurable food triggers addiction-like neuroadaptive responses in brain reward circuitries, driving the development of compulsive eating.” he said.

They also found that the levels of the D2 dopamine receptors were significantly lower in the brains of the obese animals, similar to what has been reported in human drug addicts.

And when they used a specialized virus to knock down the receptor (“lentivirus-mediated knockdown”) the addiction-like eating accelerated dramatically.

The addiction-like eating started almost as soon as they knocked down the receptors, said Kenny.

“The very next day after we provided access to the palatable food, their brains changed into a state that was consistent with an animal that had been overeating for several weeks,” he added.

Kenny and Johnson concluded that:

“These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.”

Grants from the Bank of America Fellowship, The Margaret Q. Landenberger Research Foundation and the National Institutes of Health paid for the study.

“Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats.”
Paul M Johnson and Paul J Kenny.
Nature Neuroscience, Published online 28 March 2010.
DOI:10.1038/nn.2519

Sources: Scripps Research Institute, Reuters.

Written by: Catharine Paddock, PhD