New research from the Yale School of Medicine suggests that artificial sweeteners do not fool the brain.

When investigators blocked sugar receptors in mice, they found that while the natural sugar glucose bound to the receptors despite the block, artificial sweeteners like those found in diet sodas were unable to bind. The brain’s dopamine reward system responded to glucose but not to the artificial sweetener sucralose, as well.

The finding, which appeared in the Journal of Physiology on September 23, shows that multiple systems in the brain distinguish between natural and artificial sweeteners, said senior author and professor of psychiatry at the School of Medicine Ivan de Araujo.

When administering 2-Deoxy-D-glucose, the sugar receptor blocker, researchers found that while glucose was able to successfully compete against the blocker to gain entrance to cells, the artificial sweetener, sucralose in this instance, was not. The differing successes shows that sugar receptors do not recognize artificial sweeteners as glucose, de Araujo said.

Researchers also found that post-sucralose ingestion dopamine levels remained the same as pre-ingestion levels, which stands in contrast to the rise in dopamine levels after the mice had consumed glucose.

“It’s the dopamine system telling the brain which substance is energetic and which isn’t,” said Luis Tellez, a John B. Pierce postdoctoral associate who worked on the study.

The dopamine system catches on to which foods contain high amounts of energy more quickly when the body is hungry or tired, he added.

While these findings were still in the early stages of animal experiments, some of the potential implications for humans are “exciting,” said Catherine Yeckel, a School of Public Health lecturer who also worked on the study.

With data on both sides of the artificial sweetener research, Yeckel noted this study may clarify “confusion in the literature” and help direct future studies. The research may draw attention to the issue of when these sweeteners are consumed, as opposed to merely whether they are consumed, she added.

“We tend to think of artificial sweeteners as evil. But they’re not always; it depends on the time,” Yeckel said. “This research starts to focus on when these are useful tools to employ.”

Despite popular belief, artificial sweeteners do not work as appetite suppressants, and trying to use them as such can lead to overcompensation in caloric intake later, Yeckel said. Instead of consuming them when our bodies are waiting for calories and when our glucose levels are dropping, the research suggests we may want to use artificial sweeteners at times when our bodies are less likely to notice the lack of calories, she said, pointing to times when we eat out of boredom as an example.

Essentially, we have to trick our brain and avoid the possibility that it will detect a decrease in caloric consumption, de Araujo said.

“The questions we’re trying to figure out are: What is the tolerance of the body in terms of reducing calories, but not reacting? And what’s the combination of sweetness and reduced calories that keeps the body within a certain metabolic range?” he added.

The global market for artificial sweeteners is expected to reach $1.5 billion by 2015, according to Global Industry Analysts.