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Recent studies suggest that because of their energy value, sugars are more rewarding than non-caloric sweeteners. However, intragastric infusion data indicate that sugars differ in their postoral appetite-stimulating effects. We therefore compared the preference for isocaloric 8% sucrose, glucose, and fructose solutions with that of a non-caloric sweetener solution (0.8% sucralose) in C57BL/6J mice. Brief 2-bottle tests indicated that sucralose was isopreferred to sucrose but more preferred than glucose or fructose. Yet, in long-term tests, the mice preferred sucrose and glucose, but not fructose to sucralose. Additional experiments were conducted with a non-caloric 0.1% sucralose + 0.1% saccharin mixture (S + S), which does not have the postoral inhibitory effects of 0.8% sucralose. The S + S was preferred to fructose in brief and long-term choice tests. S + S was also preferred to glucose and sucrose in brief tests, but the sugars were preferred in long-term tests. In progressive ratio tests, non-deprived and food-deprived mice licked more for glucose but not fructose than for S + S. These findings demonstrate that the nutrient-specific postoral actions, not calories per se, determine the avidity for sugar versus non-caloric sweeteners. Furthermore, sweet taste intensity and potential postoral inhibitory actions must be considered in comparing non-caloric and caloric sweeteners.

Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations.

A recent study indicated that CAST/EiJ and C57BL/6J mice differ in their taste preferences for maltodextrin but display similar sucrose preferences. The present study revealed strain differences in preferences for the constituent sugars of sucrose. Whereas B6 mice preferred 8% glucose to 8% fructose in 2-day tests, the CAST mice preferred fructose to glucose. These preferences emerged with repeated testing which suggested post-oral influences. In a second experiment, 2-day choice tests were conducted with the sugars versus a sucralose + saccharin (SS) mixture which is highly preferred in brief access tests. B6 mice strongly preferred glucose but not fructose to the non-nutritive SS whereas CAST mice preferred SS to both glucose and fructose even when food restricted. This implied that CAST mice are insensitive to the postoral appetite stimulating actions of the 2 sugars. A third experiment revealed, however, that intragastric glucose and fructose infusions conditioned significant but mild flavor preferences in CAST mice, whereas in B6 mice glucose conditioned a robust preference but fructose was ineffective. Thus, unlike other mouse strains and rats, glucose is not more reinforcing than fructose in CAST mice. Their oral preference for fructose over glucose may be related to a subsensitive maltodextrin receptor or glucose-specific receptor which is stimulated by glucose but not fructose. The failure of CAST mice to prefer glucose to a non-nutritive sweetener distinguishes this strain from other mouse strains and rats.

Adenosine triphosphate is a critical neurotransmitter in the gustatory response to the 5 primary tastes in mice. Genetic deletion of the purinergic P2X2/P2X3 receptor greatly reduces the neural and behavioral response to prototypical primary taste stimuli. In this study, we examined the behavioral response of P2X double knockout mice to maltodextrin and fat stimuli, which appear to activate additional taste channels. P2X double knockout and wild-type mice were given 24-h choice tests (vs. water) with ascending concentrations of Polycose and Intralipid. In Experiment 1, naive double knockout mice, unlike wild-type mice, were indifferent to dilute (0.5–4%) Polycose solutions but preferred concentrated (8–32%) Polycose to water. In a retest, the Polycose-experienced double knockout mice, like wild-type mice, preferred all Polycose concentrations. In Experiment 2, naive double knockout mice, unlike wild-type mice, were indifferent to dilute (0.313–2.5%) Intralipid emulsions but preferred concentrated (5–20%) Intralipid to water. In a retest, the fat-experienced double knockout mice, like wild-type mice, strongly preferred 0.313–5% Intralipid to water. These results indicate that the inherent preferences of mice for maltodextrin and fat are dependent upon adenosine triphosphate taste cell signaling. With experience, however, P2X double knockout mice develop strong preferences for the nontaste flavor qualities of maltodextrin and fat conditioned by the postoral actions of these nutrients.

Use of natural noncaloric sweeteners in commercial foods and beverages has expanded recently to include compounds from the plant Stevia rebaudiana. Little is known about the responses of rodents, the animal models for many studies of taste systems and food intake, to stevia sweeteners. In the present experiments, preferences of female Sprague–Dawley rats and C57BL/6J mice for different stevia products were compared with those for the artificial sweetener saccharin. The stevia component rebaudioside A has the most sweetness and least off-tastes to human raters. In ascending concentration tests (48-h sweetener vs. water), rats and mice preferred a high-rebaudioside, low-stevioside extract as strongly as saccharin, but the extract stimulated less overdrinking and was much less preferred to saccharin in direct choice tests. Relative to the extract, mice drank more pure rebaudioside A and showed stronger preferences but still less than those for saccharin. Mice also preferred a commercial mixture of rebaudioside A and erythritol (Truvia). Similar tests of sweet receptor T1R3 knockout mice and brief-access licking tests with normal mice suggested that the preferences were based on sweet taste rather than post-oral effects. The preference response of rodents to stevia sweeteners is notable in view of their minimal response to some other noncaloric sweeteners (aspartame and cyclamate).

Prior work has shown that sweet taste–deficient T1R3 knockout (KO) mice developed significant sucrose preferences when given long-term sugar versus water tests. The current study investigated the role of olfaction in this experience-conditioned sucrose preference. T1R3 KO and C57BL/6 wild-type (WT) mice were given 24-h sugar versus water tests with ascending concentrations of sucrose (0.5–32%), after which the mice received olfactory bulbectomy (OBx) or sham surgery. When retested with sucrose, the Sham-KO mice preferred all sugar solutions to water, although their intake and preference were less than those of the Sham-WT mice. The OBx-KO mice, in contrast, showed no or weak preferences for dilute sucrose solutions (0.5–8%) although they strongly preferred concentrated sugar solutions (16–32%). OBx-WT mice displayed only a partial reduction in their sucrose preference. Although the OBx mice of both genotypes underconsumed dilute sucrose solutions relative to Sham mice, they overconsumed concentrated sucrose. These results indicate that olfaction plays a critical role in the conditioned preference of T1R3 KO mice for dilute sugar solutions. Further, the fact that OBx-KO mice preferred concentrated sucrose solutions in the absence of normal sweet taste and olfactory sensations underscores the potency of postoral nutritive signals in promoting ingestion.

The flavor of dashi, the broth prepared from dried bonito tuna, is attractive to humans and rodents. The present experiments examined the ability of dashi to serve as an oral and/or postoral rewarding stimulus for conditioned flavor preferences in mice. In Experiment 1, C57BL/6J (B6) mice were infused intragastrically with dashi when they consumed a conditioned stimulus (CS)+ flavor and with water when they drank a CS− flavor on alternate days. Postoral dashi did not condition a CS+ prefer ence. The combined effects of oral and postoral dashi exposure were examined in Experiment 2, in which B6 mice consumed a CS+ flavored dashi solution and CS− flavored water on alternate days. The mice did not prefer the CS+ to CS− when both flavors were presented in water. Yet, the B6 mice in both experiments preferred dashi to water in oral tests. Experiment 3 showed that taste-impaired Trpm5 knockout (KO) mice did not learn to prefer dashi after exposure to it, in contrast to previous findings with the umami prototype monosodium glutamate. This was not due to an inability to taste dashi, because Trpm5 KO mice learned a strong preference for dashi after it was mixed with glucose. The impact of dashi on reward may largely reflect an enhancement of association of oral and postoral effects of food.

The consumption of monosodium glutamate (MSG) solutions has been shown to reinforce preferences for MSG and for MSG–paired flavors in mice. These effects appear to have a strong postoral component, such that MSG detected in the gut is associated with concurrently consumed flavors. Two experiments investigated postoral MSG reward by infusing 400 mM MSG intragastrically (IG) to C57BL/6 mice as they consumed a conditioned stimulus (CS+) flavor. An alternate CS− flavor was paired with IG water. In Experiment 1, the grape and cherry CS flavors were unsweetened, and intakes and preferences for the CS+ flavor were modest. Experiment 2 attempted to generate stronger preferences by adding 0.05% saccharin to the CS flavors. Sweet taste did enhance intakes during training and testing but did not significantly increase percent CS+ intake or persistence of the preference. However, only conditioning with the sweet CS+ resulted in the mice expressing a preference for oral MSG in an initial choice test with water. These findings extend recent studies demonstrating postoral MSG conditioning in rats.

The prototypic umami substance monosodium glutamate (MSG) reinforces preferences for its own flavor, as well as preferences for flavors associated with it, by conditioning processes. Mice of 3 inbred strains (C57BL/6J (B6), 129P3/J, and FVB/NJ) and 2 taste-knockout (KO) groups derived from the B6 lineage were initially indifferent to 200 mM MSG, but this evaluation was altered by forced exposure to MSG. B6 and KO mice acquired an MSG preference, 129 mice remained indifferent, and FVB mice avoided MSG. The shifts in preference imply a postoral basis for MSG effects, suggesting that it could produce preferences for associated flavors. New mice were trained with a conditioned stimulus (CS+) flavor mixed in 200 mM MSG and a CS− flavor in water . Similar to the parent B6 strain, mice missing the T1r3 element of an umami receptor or the downstream signaling component Trpm5 learned to prefer the CS+ flavor and subsequently showed similar preferences for MSG in an ascending concentration series. Consistent with their responses to forced exposure, the 129 strain did not acquire a significant CS+ preference, and the FVB strain avoided the CS+ flavor. The 129 and FVB strains showed little attraction in the ascending MSG concentration series. Together, these data indicate that the postoral effects of MSG can modulate responses to its own and MSG-paired flavors. The basis for strain differences in the responses to MSG is not certain, but the taste-signaling elements T1r3 and Trpm5, which are also present in the gut, are not required for mediation of this flavor learning.

Knockout (KO) mice missing the sweet taste receptor subunit T1r3 or the signaling protein Trpm5 have greatly attenuated sweetener preferences but learn to prefer sucrose in 24-h tests. Here, we examined 24-h preferences of T1r3 KO, Trpm5 KO, and C57BL/6J wild-type (WT) mice for glucose, fructose, galactose, and corn starch. Unlike glucose, fructose has little postoral reward effect in WT mice, whereas conflicting data have been obtained with galactose. Naive KO mice were initially indifferent to dilute glucose solutions (0.5–4%) but exhibited strong preferences for 8–32% concentrations. In a second test, they strongly preferred (~90%) all glucose concentrations although they drank less sugar than WT mice. Naive KO mice were indifferent to 0.5–8% fructose and avoided 16–32% fructose. However, the glucose-experienced KO mice displayed significant preferences for all fructose solutions. Naive KO mice preferred only 8% galactose, whereas WT mice preferred 4–16% galactose, and all mice avoided 32% galactose. Galactose experience enhanced the preference for this sugar in KO and WT mice. Naive T1r3 KO and WT mice displayed similar preferences for 0.5–32% corn starch, which were enhanced by starch experience. Naive Trpm5 KO mice did not prefer starch but did so after 1-bottle starch experience. The results confirm the sweet taste deficits of T1r3 KO and Trpm5 KO mice but demonstrate their ability to develop strong glucose and milder galactose preferences attributed to the postoral actions of these sugars. The acquired preference for the non-sweet flavor properties of glucose generalized to those of fructose. The findings further demonstrate that although Trpm5 (but not T1r3) signaling is essential for starch preference, Trpm5 KO mice can learn to prefer starch based on its postoral effects.

Female Sprague–Dawley rats display considerable variability in their preference for the artificial sweetener sucralose over water. While some rats can be classified as sucralose preferrers (SP), as they prefer sucralose across a broad range of concentrations, others can be classified as sucralose avoiders (SA), as they avoid sucralose at concentrations above 0.1 g/L. Here, we expand on a previous report of this phenomenon by demonstrating, in a series of 2-bottle 24-h preference tests involving water and an ascending series of sucralose concentrations, that this variability in sucralose preference is robust across sex, stage of the estrous cycle, and 2 rat strains (Long–Evans and Sprague–Dawley). In a second experiment involving a large sample of rats (n = 50), we established that the ratio of SP to SA is approximately 35–65%. This bimodal behavioral response to sucralose appears to be driven by taste because rats display a similar bimodal licking response to a range of sucralose solutions presented during brief-access tests. Finally, we have shown that sucralose avoidance is extremely robust as 23-h water-deprived SA continue to avoid sucralose in 1-h single-bottle intake tests. Based on their reduced licking responses to sucralose during brief-access (taste driven) tests, and the fact that their distaste for sucralose cannot be overcome by the motivation to rehydrate, we conclude that SA detect a negative taste quality of sucralose that SP are relatively insensitive to.

The preference of female Sprague-Dawley rats for sucralose, a non-nutritive sweetener derived from sucrose, was evaluated in 23 h two-bottle tests with water or saccharin. Overall, the rats displayed weak or no preferences for sucralose (0.25-4 g/l) over water but strong preferences for saccharin (0.5-8 g/l) over water and saccharin (1 g/l) over sucralose (0.5 g/l). The rats also preferred a saccharin + sucrose mixture to sucrose, but sucrose to a sucralose + sucrose mixture. There were marked individual differences in sucralose preferences: about half the rats preferred sucralose to water at some concentrations while most remaining rats avoided sucralose. Both subgroups preferred saccharin to sucralose. Sucralose appears to have an aversive off-taste that reduces its palatability to rats.

Previous research indicates that food deprivation increases the rat's preference for high-fat over low-fat foods. Since these foods differ in their flavors and post-ingestive effects, both factors may be implicated. The present study investigated preferences in food deprived and non-deprived rats using non-nutritive mineral oil emulsion (MO) and saccharin solution (SAC), which have a fatty flavor and sweet taste, respectively. The deprived rats consumed more MO than SAC in one- and two-bottle tests, while the non-deprived rats ingested as much SAC as MO in one-bottle tests and preferred SAC in two-bottle tests. Several aspects of the data suggest that the deprivation-related shift in preference between MO and SAC was determined by changes in long-term energy balance. A follow-up conditioning experiment discarded the possibility that the observed preference shift was related to differential reinforcing effects of the two substances. In conclusion, long-term food restriction increases the preference for an oily flavor over a sweet taste via a mechanism that does not involve nutritive feedback. It remains to be determined to what extent this alternation in flavor preference influences food selection when post-ingestive nutritive feedback can influence food choice.