Ghrelin linked to addictive behavior

A hormone once thought to control the release of learning and growth hormones may also induce food cravings and even other reward-associated behavior such as drug addictions, researchers at the School of Medicine reported Friday.

Discovered in 1999 and named after the Hindi word for growth, ghrelin is a hormone produced in the stomach that was previously associated with appetite, learning, memory and growth hormone release. In a paper due to be published in the December edition of the Journal of Clinical Investigation, a team of Yale Medical School researchers report that ghrelin can directly signal a part of the brain that contains reward circuitry and that may be responsible for overeating and addiction. They also found that ghrelin can activate dopamine neuronal activity, which controls reward-associated behavior to promote interest in food as a reward.

“Usually these hormones have primitive mechanisms that affect lower-brain areas such as the hypothalamus,” said comparative medicine professor Tamas Horvath, who led the project. “But here we found ghrelin binding sites even in higher level areas of the brain, such as the hippocampus. As a result, it could be linked to other, higher-level behaviors such as drug abuse.”

If further research supports the group’s findings, Horvath said, ghrelin may prove to affect a variety of behavioral areas.

“In general, anything associated with rewards is probably affected by ghrelin, be it your family or your girlfriend,” Horvath said.

Ghrelin may be an important signal from the stomach to indicate hunger and drive appetite, he said. The mechanisms by which today’s treatments for extreme obesity work, such as gastric bypass surgery, may also be related to the hormone.

Most of the research in the paper was done using mice and rats, but Horvath said similar effects are very likely to be seen in humans as well.

“These mechanisms are so primitive that we’re almost sure they’re in humans too,” he said. “In the future, we aim to do higher-level primate testing.”

The study suggests that drugs selectively targeting ghrelin pathways could be used to suppress feeding or the desire to seek out food, or even potentially to treat drug addictions, he said.

But some professors said changing public policy will do far more to deal with the obesity crisis than will the direct application of this kind of research.

Rudd Institute researcher Marlene Schwartz, who is also co-directs the Yale Center for Eating and Weight Disorders, said medication alone will not solve obesity problems.

“There’s an over-emphasis on people’s behavior, [and] we often forget how much people’s behavior is determined by external factors,” Schwartz said. “If [research] can show that products being sold to children and adults today are addictive, that could have a huge impact on obesity through public policy.”

Yale School of Medicine Dean Robert Alpern said a combination of public policy measures and individual treatment needs to be employed to combat obesity, which is the root cause of many common diseases such as diabetes.

“Drugs can help, [but] they’re not ideal,” he said. “People should eat less and exercise more — but if that doesn’t work, then we have to use medical treatment.”

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