Does trying to shed those extra pounds make you crave junk food more? Do you end up feeling deprived and bingeing on the very foods that you want to avoid? That’s the “dark side”—eating to avoid feeling nervous and moody when dieting causes neurochemical substances to be released in the brain.

“Dependence often involves not simply taking the drug to ‘get high,’ but rather to relieve the anxiety associated with abstinence,” says Pietro Cottone, assistant professor of pharmacology and psychiatry, and co-director of the Laboratory of Addictive Disorders (LAD). “When we abstain from junk food, we feel bad, anxious, and we eat to relieve the anxiety. I’m looking at different mechanisms that affect how this can happen in the brain.”

Cottone was one of 12 scientists in the country to receive the National Institute of Mental Health Biobehavioral Research Award for Innovative New Scientists in 2011. His research with LAD co-director Valentina Sabino, which shows that junk food withdrawal causes compulsive eating in rats, is controversial but compelling, given that obesity among American children and adults is reaching alarming numbers. Obesity is linked to type 2 diabetes, hypertension, and other serious health disorders.

Cottone, Sabino, and several other researchers from the National Institute on Drug Abuse, the National Institutes of Health, and the National Institute on Alcohol Abuse and Alcoholism recently published their findings in the Proceedings of the National Academy of Sciences.

In their study, one group of rats was fed unlimited regular food for five days, then a sugary, chocolate-flavored diet for two days. A second group of rats was given only regular pellet food. After consuming both pellet food and junk food for several cycles, the first group began refusing the healthier food, eating more of the sugary diet, and subsequently gaining weight. When the junk food was no longer offered, the rats acted depressed and showed signs of anxiety. Back on the regular diet, they overate, and the stress factors subsided.

“Whenever we diet, we challenge our brain.” Pietro Cottone

“The negative emotional state induced by dependence progressively increases in magnitude following every cycle of binge eating/abstinence,” says Cottone, a recipient of one of BU’s Peter Paul Career Development Professorships. “And this is what people who diet do every day. Whenever we diet, we challenge our brain.”

During withdrawal, researchers monitoring the rats’ brain activity discovered increased corticotropin-releasing factor (CRF) gene expression, a key stress neurotransmitter. Blocking the CRF receptor with a single shot of a drug named R-121919 relieved the rats’ withdrawal symptoms. The drug was previously tested in human clinical trials to treat depression, but its clinical development was discontinued due to a reversible elevation of liver enzyme activity.

Cottone and his team are building on what they’ve learned about CRF receptors to look for other drugs that might help people handle the challenges of dieting. “We know that anxiety and stress are an integral part of the maintenance of drug dependence, and now we have evidence that they play an important role in compulsive eating as well,” he says. “So we know who the bad guy is, and it’s a potential pharmacological target.”