Sugar addiction in rats may shed light on human behavior

Hoebel and researchers in the department of psychology and the Princeton Neuroscience Institute have demonstrated patterns of craving and relapse, the third and final stage of addiction, that had previously gone unobserved in rats. Though the stages of increased intake and withdrawal have been documented, craving and relapse provide the missing link in establishing sugar as an addictive substance for rats.

Hoebel, who joined the Princeton faculty in 1963, undertook the study with visiting researchers Nicole Avena GS ’06 and Pedro Rada from the University of Los Andes in Venezuela. The three have submitted their research in a paper to the Journal of Nutrition.

This discovery could have salient implications on the study of sugar addiction in humans. “As far as humans are concerned, there’s no good scientific evidence yet,” Hoebel said. “However, there are many books on sugar addiction and websites on sugar addiction as well as millions if not billions of people who would classify themselves as sugar addicts, so I’m sure this is something that will be looked at with great interest in the near future.”

Avena noted the need to proceed with caution when extrapolating this pattern of sugar addiction to humans.

“I think that the research is a good start to understanding what is going on in terms of the neural mechanisms underlying overeating and perhaps obesity,” Avena said. “Our research has been done primarily in rats, so we have to be careful in terms of how we interpret the data. Based on the findings we do have in rats, it does suggest that certain foods, namely sugar, may have some addictive-like characteristics.”

During the abstinence stage, in which rats were denied sugar but given as much food as they desired for 10 days, rats showed withdrawal signs that suggested anxiety, which was measured through behavioral tests.

Hoebel explained in an interview that when sugar was reintroduced 10 days later, the rats’ brains were still not back to normal. At this point, the craving-and-relapse-stage rats who have “learned to bar press for their sugar, now ... bar press for their sugar again, but more than ever before,” Hoebel said, adding that “abstinence makes the heart grow fonder, right? Being on a sugar-free diet didn’t help them. This triggers relapse, and they go back to bingeing again.”

Moreover, the rats’ increased consumption of other addictive substances, reflecting neurochemical changes in their brain function, parallels their intensified appetite for sugar. “In certain models, sugar-bingeing causes long-lasting effects in the brain and increases the inclination to take other drugs of abuse, such as alcohol,” Hoebel explained in a University statement. He said that the behavioral study was carried out in addition to a neuroscientific approach, in which he and his team observed the release of dopamine, a neurotransmitter involved in reward motivation. Repeated release of dopamine, which precipitates a rewiring of the rats’ brain, is believed to cause addiction.

To produce a phenomenon analogous to human binge eating, the excessive intake of food all at once, Hoebel and his team deprived the rats of food for four hours after they awoke from sleeping. “It’s pretty much the same thing as missing breakfast for us,” Hoebel said. Rats would then quickly eat some food and drink above-average quantities of 10 percent sucrose solution, which Hoebel compared to a soft drink.

Hoebel and his team intend to investigate if there is a link between eating disorders and sugar addictions and aim to study whether non-nutritive sweeteners like saccharin and high-fructose corn syrup produce the same effect, as those are the substances that are really impacting the obesity epidemic, Hoebel said.. “[High-fructose corn syrup is] what’s really in soft drinks these days,” Hoebel explained in an interview.

Avena plans to look at the genetic underpinnings of addiction. “My research interests lie in looking at some of the neural and molecular mechanisms underlying binge eating and perhaps understanding, on a level of gene expression, how certain changes can be involved in binge eating that may be related or similar to those that we see with drug addiction,” she said.