Food Reward in the Absence of Taste Receptor Signaling

To test this hypothesis, Ivan de Araujo and colleagues at Duke University have studied the behavioral and brain responses to caloric sucrose solutions in mice lacking the cellular components of taste cells required for the perception of sweet taste.

In 2003, Charles Zuker (at the University of California in San Diego) and Nicholas Ryba (at NIH) have shown that mice lacking the gene that encodes for a protein known as "trpm5" - highly expressed in taste cells - are "sweet-blind", that is do not detect or show any preferences for sweet tastes. These animals were used by de Araujo and colleagues to study longer-term preferences for sweet compounds.

After confirming that these animals in fact ignored the palatability of sucrose solutions (unlike "wild-type" animals, that is animals that do express the trpm5 protein on the tongue), the researches designed an experiment where sippers containing either caloric sucrose solutions or plain water were placed at different locations of the behavioral cages, during alternate days. So on one particular day a sipper containing sucrose was placed for example on the left side; on the next day water was placed on the right side (daily sessions took 30 min) and so on.

Strikingly, de Araujo and colleagues observed that, over the course of training days, the animals developed a preference for drinking from the sipper that contained sucrose despite showing an initial indifference to it. Furthermore, on a final testing session, two bottles containing water were offered to the animals, and in fact they have in in this occasion consumed almost exclusively from the side of the cage that had been previously associated with caloric sucrose.

Next, the researchers performed the same experiment on a new group of animals, but this time substituting sucrose for sucralose, a highly palatable sucrose-derived sweetener (commercially available as "Splenda") that nonetheless is not absorbable by the intestine and thus provides no calories. This time, while wild-type animals slurped the sucralose solutions, sweet-blind mice essentially ignored it and did not develop any preferences towards it. de Araujo and colleagues then ascribed the previously observed results to the caloric content of sucrose alone.

Next, the researchers inquired about what brain processes might underlie this phenomenon. It is well established that palatable compounds, including sweet tastes or fat, can activate the so called "brain reward systems" even when no calories are being absorbed. In particular, the chemical dopamine is secreted by brain cells when animals, and humans, experience tasteful compounds. The role of this region in food intake had thus been ascribed to detecting the hedonic oral component of foods.

The researches however guessed that calories per se, even in the absence of taste, could activate reward brain regions - in fact, de Araujo reasoned, the sense of taste did not evolve to provide us with pleasant moments to be remembered, but rather to help us finding calories in nature in an efficient way. The actual reward that matters, that is the one that will help survival, is calories not taste. So they tested the hypothesis that dopamine would be released in the brain of sweet-blind animals after they consumed sucrose, but not sucralose. Using a technique called brain microdialysis, the researchers collected samples of brain fluids from wild-type and sweet-blind animals while drinking the different solutions.

As expected, wild-type animals showed\d increases in brain dopamine levels after during both sucralose (i.e. no calories) and sucrose drinking; however, sweet-blind animals showed increases in dopamine levels only after drinking sucrose, while the response to sucralose was undetectable. The researches then concluded that there must be two pathways through which caloric compounds stimulate brain reward regions, one that is dependent on taste information and a second that is not. These findings were later confirmed by measuring the electrical activity of the brain reward system in similar situations.

Overall, the results mean that calories per se, independently of taste sensation, can stimulate reward brain regions and thus drive consumption of caloric foods. Therefore, the amount of "pleasantness" that we associate with particular foods depends not exclusively on taste, but also - on a longer time frame - on the post-ingestive consequences of having consumed that food. This finding might explain why diets based on low-caloric but tasteful components might lead to calorie overconsumption from other sources, as was recently shown by S. Swithers and T. Davidson from Purdue University, who found that consumption of products containing artificial sweeteners may lead to increased body weight and obesity.

Reference:

de Araujo, I; Oliveira-Maia, A; Sotnikova, T, et al. "Food Reward in the Absence of Taste Receptor Signaling", Neuron, Vol 57, 930-941, 27 March 2008. Abstract available here.