Flavor preferences conditioned by nutritive and non-nutritive sweeteners in mice

Abstract

Recent studies suggest that preferences are conditioned by nutritive (sucrose) but not by non-nutritive (sucralose) sweeteners in mice. Here we compared the effectiveness of nutritive and non-nutritive sweeteners to condition flavor preferences in three mouse strains. Isopreferred sucrose and sucralose solutions both conditioned flavor preferences in C57BL/6J (B6) mice but sucrose was more effective, consistent with its post-oral appetition action. Subsequent experiments compared flavor conditioning by fructose, which has no post-oral appetition effect in B6 mice, and a sucralose + saccharin mixture (SS) which is highly preferred to fructose in 24-h choice tests. Both sweeteners conditioned flavor preferences but fructose induced stronger preferences than SS. Training B6 mice to drink a flavored SS solution paired with intragastric fructose infusions did not enhance the SS-conditioned preference. Thus, the post-oral nutritive actions of fructose do not explain the sugar’s stronger preference conditioning effect. Training B6 mice to drink a flavored fructose solution containing SS did not reduce the sugar-conditioned preference, indicating that SS does not have an off-taste that attenuates conditioning. Although B6 mice strongly preferred flavored SS to flavored fructose in a direct choice test, they preferred the fructose-paired flavor to the SS-paired flavor when these were presented in water. Fructose conditioned a stronger flavor preference than an isopreferred saccharin solution, indicating that sucralose is not responsible for the limited SS conditioning actions. SS is highly preferred by FVB/NJ and CAST/EiJ inbred mice, yet conditioned only weak flavor preferences. It is unclear why highly or equally preferred non-nutritive sweeteners condition weaker preferences than fructose, when all stimulate the same T1r2/T1r3 sweet receptor. Recent findings support the existence of non-T1r2/T1r3 glucose taste sensors; however, there is no evidence for receptors that respond to fructose but not to non-nutritive sweeteners.

The Effect of Nonnutritive Sweeteners Added to a Liquid Diet on Volume and Caloric Intake and Weight Gain in Rats

“…This finding has particular credence when compared to studies that fail to report caloric intakes . The absence of an increased caloric intake, despite the appeal of the sweet taste, may be related to the inability of NNS to produce appetition, combined with the postingestive inhibitory effects of the other nutrients, which are identical in these diets .…”

A gut sensor for sugar preference

“…Concentrations were selected based on prior studies showing iso-sweetness. 53,54 The side of the sucrose and sucralose solutions was swapped each test to control for side preferences. In order to advance to optogenetic or pharmacologic inhibition, mice were required to display a stable preference for sucrose, defined as > 66% sucrose preference in two consecutive tests, not varying by more than 15% across both tests.…”

Taste Processing: Insights from Animal Models

“…The ability to distinguish between different tastes is a learning related to survival. For example, the sweet taste of saccharin or glucose, which provides high calories and therefore energy [23,24], induces dopamine release in the reward system of the brain [25,26]. This system makes it possible to learn taste preferences as an adaptive mechanism in nature.…”