Researchers find different pathways responsible for sugar addiction and healthy eating

MIT researchers are on the way to fully identifying the neurological underpinnings of sugar addiction (Image: MIT) Many who have tried to kick the sweet white crystals will tell you that "sugar addiction" is very real, and there are indeed neurological underpinnings that back them up. MIT researchers have now discovered that the pathways of the brain responsible for sugar addiction may differ from those which govern drug addiction and healthy eating, which could be a boon for studies and treatment of compulsive eating and obesity. According to the researchers, solving a person’s “addiction” (emphasis theirs) to sugar is more complicated than solving drug addiction as it requires reducing a drive to eat unhealthily, rather than simply reducing the drive to eat. In fact, feeding and drug addiction drives are different things even though they stem from the same areas of the brain. The neuroscientists discovered that inhibiting a certain brain circuit could limit the desire to consume excess sugar without harming a regular, healthy appetite. Their process to reach this is not only rather fascinating but tells us much about how the brain regulates cravings and can even be trained to trigger or cancel a craving. “For the first time, we have identified how the brain encodes compulsive sugar seeking and we’ve also shown that it appears to be distinct from normal, adaptive eating,” says Kay Tye, the Whitehead Career Development Assistant Professor in MIT's Department of Brain and Cognitive Sciences. The brain has a reward-processing center called the ventral tegmental area (VTA), which is located in the midbrain and plays a major role in drug addiction, orgasm, intense emotions related to love and cognition, among other things. Drugs interfere with its normal processing, however the quandary here is that food is not an artificial reward like a drug is, but a very natural one. Interestingly, there also seems to be a link between blood sugar levels and nicotine, with the former helping to release the latter, resulting in the small high that smokers can experience. Scientists then looked at the connections between the VTA and the lateral hypothalamus (LH). The LH was chosen as it controls, among many other things, feeding behavior in general. However, the actual circuit that controls and rewards feeding behavior in particular had not yet been isolated by anyone. Tye and graduate student Edward Nieh identified and then characterized the particular LH neurons that connected to the VTA, first recording neuron activity in brain slices before moving onto live mice models where they used electrodes. The mice were specially trained to get their sucrose – which mice actually love – at a certain point when they heard and saw a cue. So far, so Pavlovian. Once the mice had learned to predict their "reward" it was randomly withheld, whilst other times it was delivered unexpectedly without the usual heralding. What did the bait-and-switch achieve? Something rather interesting. A certain kind of LH neuron that connects to the VTA only became active after learning to seek a food reward, whether it was provided or not. After receiving feedback from the VTA, another set of LH neurons encoded the response to the reward or to its omission. It seems the addiction path: action, habit, compulsion can actually be traced in the identified LH-VTA circuit. The neural projections in the mice were then modified to carry light sensitive proteins that are able to activate or stop neurons with pulses of light. When activated, the mice began to compulsively eat sucrose, past the point of satiety. However, when this was deactivated the mice stopped their overeating, but only of sucrose. Their regular appetite was not affected. "That was exciting because we have the recording data to show how this compulsive sugar-seeking happens," says Nieh. "And we can drive or suppress just the compulsive behavior by making very precise changes in the neural circuit." These same neurons send excitatory and inhibitory signals to the VTA and it is the latter which actually, surprisingly, inspire the animal's cravings. This may change the way clinicians treat compulsive overeating, something that in an increasingly obese world, is a good, even revolutionary, thing. "This study represents an outstanding step forward in understanding the many intricate aspects of feeding behaviors," says Antonello Bonci, who wasn't involved in the research but is the scientific director at the National Institute on Drug Abuse. "The extraordinary multidisciplinary approach used in this study produced a very exciting finding: that compulsive sugar consumption is mediated by a different neural circuit than physiological, healthy eating." So far, the team's work has only focused on mice and more study is needed, but they are hopeful their findings will pave the way to developing safe techniques for combating sugar addiction. Their research was recently published in the journal Cell Source: MIT