From the abstract of their paper, the two researchers’ goal was thus: "These experiments were designed to test the hypothesis that experiences that reduce the validity of sweet taste as a predictor of the caloric or nutritive consequences of eating may contribute to deficits in the regulation of energy by reducing the ability of sweet-tasting foods that contain calories to evoke physiological responses that underlie tight regulation."

They fed them yogurt that was sweetened either with the natural sweetener glucose (simple sugar) or the artificial sweetener saccharin. The researchers gave both groups of rats an unrestricted supply of food and water.

After five weeks on this diet, the researchers found that the artificial-saccharin fed mice had eaten more calories, gained more weight, and produced more body fat than their natural-glucose-fed counterparts.

Specifically, Swithers and Davidson discovered “that reducing the correlation between sweet taste and the caloric content of foods using artificial sweeteners in rats resulted in increased caloric intake, increased body weight, and increased adiposity, as well as diminished caloric compensation and blunted thermic responses to sweet-tasting diets. These results suggest that consumption of products containing artificial sweeteners may lead to increased body weight and obesity by interfering with fundamental homeostatic, physiological processes.”

Swithers and Davidson concluded that natural sweeteners provide humans and rats with a signal that they are eating food and when their stomachs are full of food. With artificial sweeteners, like saccharin, there is no signal sent predicting how much food is eaten, so the animal eats more food.

Thus, the number of calories is better regulated with natural means than artificial ones.

This regulation has evolved over time so that animals, like humans, associate natural sweetness with caloric intake. When that natural association is taken away (with the use of artificial sweeteners), these animals have no clue as to how much food they are eating, so eat more.

The  result of Swithers and Davidson’s research study is written up in the journal Behavioral Neuroscience under the title “A Role for Sweet Taste: Calorie Predictive Relations in Energy Regulation by Rats” (2008, Volume 122, no. 1, pages 161-173).