The use (and misuse) of nonnutritive sweeteners in studies of sugar appetite and reward in rodents

Auteur(s): Sclafani A, Ackroff K, Glendinning JI.
Nom de la publication : Physiol Behav. 2026 Apr 7:115332. https://doi.org/10.1016/j.physbeh.2026.115332
Année de publication : 2026

Abstract:

Dietary sugars are highly attractive and promote eating and, in some cases, overeating and obesity. In addition to sweet taste, sugars have postoral actions that activate brain reward circuits that further enhance sugar appetite and consumption. Nonnutritive sweeteners (NNSs) share the sweet taste but not the postoral appetition actions of sugars. NNSs are a useful research tool to investigate the oral and postoral reward effects of sugars in humans and laboratory rodents. Contemporary studies with sugars and NNSs have facilitated the discovery of sugar-specific gut sensors and gut-brain pathways that mediate postoral sugar reward. At times, however, NNSs have been misused in rodent studies. First, sugar and NNS (e.g., saccharin and sucralose) solutions are often assumed to be « isosweet » to rodents based on human sweetness ratings. The sweetness potency of NNSs, however, is much reduced in rodents compared to humans. Second, some studies use NNSs (e.g., aspartame) that evoke sweet-like tastes in humans but not in rodents. Third, other studies use commercial NNS formulations that contain a carbohydrate filler (e.g., maltodextrin). Investigators assume that the NNSs alone are stimulating intake, and overlook the attractive taste and postoral actions of the carbohydrate filler. We review rodent studies that used NNSs to investigate the oral and postoral reward actions of sugars, and highlight the findings that were based on appropriate or inappropriate applications of NNSs.

 

Summary:

This study examines how dietary sugars and low/no calorie sweeteners (LNCS) influence appetite and reward in rodents. It emphasises that while sugars are highly attractive due to the combination of their sweet taste and postoral effect that activate brain reward systems, LNCS generally lack these postoral reinforcing properties while still providing a sweet taste, making them useful tools for separating taste-driven versus nutrient-driven effects.

The authors argue that LNCS are often misused in rodent studies. Common methodological issues include comparing sugar and LNCS solutions that differ in palatability, using LNCS that rodents do not perceive as sweet – such as aspartame, and relying on commercial sweetener products containing caloric fillers. The authors conclude that a careful experimental design is essential for generating valid insights into sugar appetite and reward mechanisms.

Given that rodent studies are frequently used to inform understanding of the effects of LNCS on human appetite, metabolism, and obesity risk, flawed study designs can lead to misleading conclusions about whether LNCS satisfy reward, increase cravings, or alter eating behaviour.

 

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