BUSM researchers show dieters can experience neurobiological similarities of drug addicts

(Boston) — Researchers from Boston University School of Medicine (BUSM) have shown
that intermittent access to foods rich in fat and sugar induces changes in the brain which are comparable to those observed in drug dependence. The findings, reported in the journal Proceedings of the National Academy of Sciences, may explain how abstinence from these foods contributes to relapse eating among dieters as well as related eating disorders.

Forms of obesity and eating disorders can be defined as chronic relapsing conditions with alternating periods of abstinence (dieting to avoid “forbidden” foods-rich in sugar and fat also known as palatable foods) and relapse (compulsive, often uncontrollable, eating of highly-palatable foods) that continue despite negative consequences. Although the positive reinforcing properties of palatable foods are well known, less attention has been given to the increased probability of a behavioral response produced by removal of an aversive stimulus (intake of palatable food to relieve negative emotional states).

The researchers used 155 rats to measure the neurobiological responses. The first group, the diet cycled subjects, repeatedly ate standard rat chow for five days, followed by a highly palatable, high-sugar, chocolate-flavored chow for two days. The second group ate only standard food. The amount of food consumed was not restricted for either group. When the diet-cycled rats were fed standard chow, they showed less motivation to obtain it, refused it, although it was previously acceptable, and they exhibited anxiety. However when the rats resumed eating the palatable food, they overate and their anxiety-related behaviors returned to normal.

The researchers then looked at the role of the brain’s stress system, which contributes to cycles of drug and alcohol binging and withdrawal, in driving these behaviors. They found that during abstinence from palatable foods, the rats showed increased corticotropin-releasing factor (CRF) gene expression and peptide in the amygdala, an area of the brain involved in fear, anxiety and stress responses. Similar to the anxiety, only when the diet-cycled group was fed palatable food did CRF levels return to normal. Importantly, the blockade of the CRF receptor 1 with a selective antagonist was able to prevent all the behavioral outcomes of palatable food withdrawal.

According to the researchers, CRF is a key stress neurotransmitter. “In observing the activation of the amygdaloid CRF system during abstinence from palatable foods, we understood the causes of recurrent dieting failures,” said study co-author Pietro Cottone, PhD, an assistant professor and co-director of the Laboratory of Addictive Disorders in the Department of Pharmacology and Experimental Therapeutics at BUSM.

“CRF activation during abstinence from palatable foods induces a negative emotional state which is responsible for signs of anxiety and contributes to relapse to ‘forbidden foods,'” added study co-author Valentina Sabino, PhD, an assistant professor and co-Director of the Laboratory of Addictive Disorders in the Department of Pharmacology and Experimental Therapeutics at BUSM. “The stress experienced by frequent dieters in abstinence from palatable food has neurobiological similarities to the negative emotional state of drug and alcohol addicts.”

In addition to 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, George Koob and Eric Zorrilla from the Scripps Research Insitutute; 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.

This study was supported by the National Institute on Drug Abuse; the National Institute on Alcohol Abuse and Alcoholism; the National Institute of Diabetes and Digestive and Kidney Diseases; the Pearson Center for Alcoholism and Addiction Research; the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism.

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