"People will often say they are eating bad foods or fail a diet because they 'are stressed,'" he said. "Our findings suggest that intermittently eating sweet food changes the brain's stress system so that you might feel stressed, even though nothing that terrible has happened. In other words, you might be self-medicating stress-like symptoms of abstinence with that piece of pie. Or, the adaptations in your brain stress system might make you more reactive to otherwise minor stressors."

To confirm these results and to see whether blocking CRF could reverse some of the effects of diet cycling, the researchers turned to a compound called R121919 (a small molecule CRF1 receptor antagonist).

When administered to the diet-cycled rats, the compound blunted the bingeing on sweet chow, as well as the lackluster pursuit of regular chow and the anxiety-associated behaviors during this part of the diet cycle. As in similar studies modeling alcoholism, on a molecular level diet-cycled rats showed greater sensitivity to the ability of the CRF1 receptor antagonist to reduce central amygdala synaptic transmission of the neurotransmitter GABA, which plays an important role in regulating neuronal excitability.

"We believe we may have identified part of the neurochemical basis underlying behavioral adaptations that can result from yo-yo dieting," said Zorrilla. "The mechanism corresponds to what is colloquially known as the 'dark side' of addiction to drugs of abuse or ethanol, supporting the idea that the brain shows addiction-like adaptations to intermittent eating of palatable food."

While many questions remain, the study helps explain how a pattern yo-yo dieting can be established and why it is usually ineffective in promoting weight loss. The study also underlines the health risks of such an eating pattern, as activation of the brain's stress system has been linked not only to emotional disorders, but also to conditions such as heart disease.

"The findings suggest that frequent dieting with frequent relapse is worse than dieting by itself," said Cottone.

In addition, the research opens the door to potential development of a drug therapy to assist people escape an unhealthy cycle of eating.

In addition to Zorrilla, Cottone, and Sabino, the paper, "CRF system recruitment mediates dark side of compulsive eating," was authored by Marisa Roberto, Michal Bajo, Lara Pockros, Jennifer B. Frihauf, Eva M. Fekete, Bruno Conti, and George Koob of Scripps Research; Luca Steardo of the University of Roma La Sapienza (Rome, Italy); Kenner C. Rice of the National Institute on Drug Abuse of the National Institutes of Health (NIH); and Dimitri E. Grigoriadis of Neurocrine Biosciences.

Source: Scripps Research Institute