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. 2017 Feb 3;42(3):259–267. doi: 10.1093/chemse/bjx003

CAST/EiJ and C57BL/6J Mice Differ in Their Oral and Postoral Attraction to Glucose and Fructose

Anthony Sclafani 1,✉, Austin S Vural 1, Karen Ackroff 1
PMCID: PMC6075621  PMID: 28158517

Abstract

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.

Keywords: flavor conditioning, fructose, glucose, saccharin, strain differences, sucralose

Introduction

Inbred mouse strain differences in taste and nutrient preferences are well known. For example, some strains are indifferent to nutritive and non-nutritive sweeteners at low concentrations while others display significant preferences (Bachmanov et al. 2014). These differences are attributed in large part to genetic variations in the gene that codes for the T1r3 protein, which combines with the related T1r2 to form the T1r2/T1r3 sweet taste receptor (Bachmanov et al. 2014). More recently, Poole et al. (2016) reported strain differences in the preference for maltodextrin, a glucose polymer that has an attractive, but nonsweet taste to rodents. Among the differences they observed, CAST/EiJ (CAST) mice displayed a weak avidity for maltodextrin compared to C57BL/6J (B6) mice, although both strains displayed strong sucrose preferences consistent with the high saccharin preferences observed in these strains (Reed et al. 2004). Maltodextrin avidity is mediated by a taste receptor separate from the T1r2/T1r3 sweet receptor as indicated by the maltodextrin preferences displayed by the sweet ageusic T1r2 and T1r3 receptor knockout mice (Treesukosol et al. 2009, 2011; Zukerman et al. 2009; Treesukosol and Spector 2012). Poole et al. (2016) hypothesized that CAST mice, along with another strain (PWK/PhJ), have less sensitive forms of the yet to be identified maltodextrin taste receptor compared to B6 mice.

CAST and B6 strains also differ in their preferences for high-fat versus high-carbohydrate diets (Smith et al. 2000): CAST mice consume more of their energy as carbohydrate, whereas B6 mice preferentially consume fat. We confirmed these strain differences in fat and carbohydrate preferences as well as in maltodextrin but not sucrose preferences (Sclafani et al. 2016b). We also observed dramatic differences between CAST and B6 mice in their preferences for glucose and fructose, which are the constituent monosaccharide sugars in sucrose. Whereas B6 mice preferred glucose to fructose, CAST mice preferred fructose to glucose. This was unexpected given that, as mentioned above, B6 and CAST mice display strong preferences for sucrose and saccharin (Reed et al. 2004; Poole et al. 2016). Sugar intake and preference are controlled not only by oral taste receptors but also by postoral sugar sensors (Sclafani and Ackroff 2012b). In particular, we have reported that intragastric (IG) sugar infusions can increase the intake of and preference for flavored solutions, via a process referred to as appetition to distinguish it from the satiation process that inhibits sugar intake (Sclafani and Ackroff 2012b; Sclafani 2013). It may be that CAST and B6 mice differ in their glucose versus fructose preferences because of differences in their post-oral appetition responses to these sugars. We have observed differences in postoral sugar appetition with other inbred strains. In particular, whereas B6 and FVB mice show robust appetite stimulation with IG glucose infusions, only FVB mice display appetite stimulation with IG fructose infusions (Sclafani and Ackroff 2012a; Sclafani et al. 2014). Nevertheless, FVB mice, like B6 mice, prefer glucose to fructose in 24-h choice tests, consistent with the finding that glucose has a stronger postoral appetition effect than fructose in FVB mice (Sclafani et al. 2014). Conceivably, the postoral appetite stimulating effect of fructose is stronger than that of glucose in CAST mice, which would account for their acquired fructose preference. This would be a novel finding because in other rodents glucose preference and appetition exceeds that of fructose (B6, FVB, SWR, and BALB mice, and Sprague-Dawley, Long-Evans, and Wistar rats) (Ackroff and Sclafani 1991a, 1991b; Ramirez 1996; Ackroff et al. 1997; Flaherty and Mitchell 1999; Tonosaki 2010; Sclafani et al. 2014; Sclafani et al. 2015; Kraft et al. 2016; Wakabayashi et al. 2016). The present study investigated glucose and fructose appetition in CAST and B6 mice by comparing their preferences for the 2 sugars in 2-bottle choice tests, in choice tests with each sugar versus a non-nutritive sweetener, and in tests with flavored solutions paired with IG sugar infusions.

Experiment 1: Glucose versus fructose preferences

Our recent findings of opposite sugar preferences in CAST and B6 mice were obtained with animals that had extensive prior experience with fat, sucrose, and maltodextrin, which may have influenced their response to glucose and fructose. In Experiment 1, therefore, we compared fructose versus glucose preferences in CAST and B6 mice that were naïve to nutritive solutions. After separate tests with each sugar versus water, the mice were retested for their glucose versus fructose preference to determine if it is modified by experience.

Materials and methods

Animals

Male CAST/EiJ (n = 9) and C57BL/6J mice (n = 10) obtained from Jackson Laboratories at 8 weeks old were adapted to the laboratory for 1 week. The CAST mice weighed significantly less than B6 mice at the start of the experiment [14.6 vs. 23.9 g, t(17) = 18.1, P < 0.001], which is characteristic of these 2 strains. The mice were singly housed in plastic tub cages in a room maintained at 22 °C with a 12:12 h light-dark cycle and given ad libitum access to chow (5001, PMI Nutrition International) and water except where noted. Experimental protocols were approved by the Institutional Animal Care and Use Committee at Brooklyn College and were performed in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.

Test solutions

Sugar solutions (8%) were prepared using food-grade glucose and fructose (Tate and Lyle, Honeyville Food Products) and deionized water. They were formulated on a w/w basis because intakes were measured by weight.

Procedure

Two-day choice tests were conducted in the home cages. The solutions were available through stainless steel sipper spouts attached to 50-mL plastic tubes that were placed on the grid top of the cage. The 2 sipper spouts were inserted through holes positioned 3.7 cm apart, and the drinking tubes were fixed in place with clips. Fluid intakes were measured to the nearest 0.1 g by weighing the drinking bottles on an electronic balance interfaced to a laptop computer. Intakes were corrected for spillage, which was estimated by recording the change in weight of 2 bottles that were placed on an empty cage. The mice were given 2-bottle access to water for 5 days to familiarize them to the choice tests.

The mice were given a series of 2-day, 2-bottle choice tests as follows: Test 1 (days 1–2) 8% fructose versus 8% glucose; Test 2 (days 3–4) 8% glucose versus water, Test 3 (days 5–6) 8% fructose versus water, and Test 4 (days 8–9) 8% fructose versus 8% glucose. The mice were given water only on day 7 prior to Test 4 to make it comparable to Test 1, which was preceded by water only access. The left-right positions of the sugar and water bottles were switched from the first to second day of each test.

Daily fluid intakes were averaged over the 2 days of each test and sweetener preferences were expressed as percent solution intakes (e.g., fructose intake/total intake × 100). Intakes were analyzed using a mixed model analysis of variance (ANOVA) with test and solution as repeated factors. One ANOVA included results from Tests 1 and 4 and determined if the relative intakes of the 2 sugars changed across the 2 tests. A second ANOVA included results from Tests 2 and 3 and compared the preference for each sugar over water. Additional ANOVAs are described below. Percent sweetener intakes were analyzed with t-tests.

Results and discussion

The CAST mice were indifferent to glucose and fructose in Test 1 but consumed significantly (P < 0.01) more fructose than glucose in Test 4 [sugar × test interaction, F(1, 8) = 27.1, P < 0.001] (Figure 1). Their percent fructose intake increased from 44% to 72% from the first to last test [t(8) = 4.8, P < 0.01]. In the sugar versus water Tests 2 and 3, the CAST mice consumed more sugar than water [P < 0.001] and also consumed more glucose than fructose [solution × test, F(1, 8) = 9.1, P < 0.05]. In contrast, the B6 mice consumed more glucose than fructose in both Tests 1 and 4 [F(1, 9) = 67.7, P < 0.001] although their glucose intake increased from the first to last test [sugar × test interaction, F(1, 9) = 17.8, P < 0.01] (Figure 1). Their glucose preference also increased from 70% to 95% in Tests 1 and 4 [t(9) =3.6, P < 0.01]. In Tests 2 and 3, the B6 mice consumed more sugar than water [F(1, 9) = 502.3, P < 0.01] and also consumed significantly more (P < 0.01) glucose than fructose [sugar × test interaction, F(1, 9) = 64.1, P < 0.001]. Between group comparisons indicated that the groups did not differ in their Test 1 sugar intakes but that the CAST mice consumed more fructose and less glucose than did the B6 mice in Test 4 [group × sugar × test interaction, F(1, 17) = 41.4, P < 0.001]. The 2 groups consumed similar amounts of glucose in Test 2 while the CAST mice consumed more (P < 0.01) fructose than B6 mice in Test 3 [group × sugar × test interaction, F(1, 17) = 8.8, P < 0.01].

Figure 1.

Figure 1.

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Experiment 1. Mean intakes (+SEM) of sugar and water in 2-day, 2-bottle tests in CAST (left panel) and B6 mice (right panel). (Order of testing is from left to right in the panels.) In Tests 1 and 4, the mice were given the choice of 8% fructose versus 8% glucose. In Test 2, the choice was glucose versus water and in Test 3, it was fructose versus water. Numbers atop bars represent mean percent preference for that solution. Significant (P < 0.05) intake differences within the 2-bottle tests are indicated by an asterisk (*).

Consistent with our prior results (Sclafani et al. 2016b), the CAST mice consumed more fructose than glucose while the B6 mice consumed more glucose than fructose in the sugar versus sugar tests. In Test 1, however, the CAST mice were indifferent to the 2 sugars and their significant fructose preference did not emerge until Test 4 following the separate sugar versus water tests. In contrast, the B6 mice preferred glucose in Test 1 and increased in their preference in Test 4. The enhanced, albeit opposite preferences both strains displayed in Test 4 suggest a learned response based on experience with the taste and postoral actions of the sugars in Tests 2 and 3. In the case of the B6 mice, rapid post-oral learning appeared to occur in Test 1. On day 1 of the test the B6 mice displayed a 56% glucose preference which increased (P < 0.001) to 79% on day 2. In contrast, the percent glucose intakes of the CAST mice were identical (56%) on the 2 days of Test 1.

In Tests 2 and 3, the CAST and B6 mice strongly preferred both sugars to water although both strains consumed more glucose than fructose. The elevated intake and strong preference for glucose displayed by the B6 mice is consistent with prior findings demonstrating that IG glucose but not fructose stimulates intake and conditions strong flavor preferences in this strain (Sclafani and Ackroff 2012a). Why CAST mice consumed more glucose than fructose but yet strongly preferred fructose in Test 4 is not clear. The lack of preference for glucose over fructose in Test 1 indicates that the CAST mice did not inherently prefer fructose. Conceivably, glucose was less satiating than fructose to CAST mice and thus induced greater intakes, but this is not supported by subsequent findings as discussed below.

The finding that CAST mice consumed as much or more sugar as did the B6 mice in Tests 1–4 is remarkable given that they weighed 40% less than did the B6 mice. On a body weight basis, the CAST mice consumed substantially more sugar than the B6 mice. For example, the 2 strains consumed similar absolute amounts of glucose in Test 2 (22.6 vs. 23.9 g/day), but the CAST mice consumed significantly more glucose than B6 mice per 20 g body weight [31.1 vs. 19.9, t(17) = 6.3, P < 0.001]. This is consistent with the prior report that CAST and B6 mice consumed similar amounts of 4% sucrose although the CAST mice weighed much less than B6 mice (Poole et al. 2016).

Experiment 2: Fructose and glucose versus sucralose + saccharin preferences

The strong glucose preference displayed by the B6 mice in the first experiment is consistent with prior findings that glucose has a more potent postoral appetite stimulating action than fructose in this strain (Sclafani and Ackroff 2012a; Zukerman et al. 2013a). The opposite sugar preference displayed by CAST mice suggests that their postoral fructose appetition exceeds that of glucose. A simple method for evaluating postoral sugar appetition is to compare sugar versus non-nutritive sweetener preferences in long-term tests. In 1-min choice tests, B6 mice strongly prefer a 0.1% sucralose + 0.1% saccharin mixture (SS) to 8% glucose and 8% fructose, but develop a strong preference for 8% glucose but not fructose over the non-nutritive SS in 2-day tests (Sclafani et al. 2015, 2016a). In contrast, FVB mice come to prefer fructose to SS, although they display an even stronger preference for glucose over SS (Sclafani et al. 2014). This is consistent with findings that IG fructose and, to a greater extent, IG glucose infusions condition flavor preferences in FVB mice (Sclafani et al. 2014). In the present experiment, we compared the fructose and glucose preferences relative to non-nutritive SS in CAST and B6 mice. We expected that CAST mice would prefer fructose to SS more so than glucose to SS while the opposite pattern would be displayed by B6 mice.

Materials and methods

The mice from the first experiment were given 3 series of 2-day choice tests with 8% sugar versus a mixture of 0.1% sucralose (Tate & Lyle) and 0.1% sodium saccharin (Sigma–Aldrich). The first series consisted of: Test 1 (days 1–2) fructose versus SS, Test 2 (days 3–4) fructose versus water, Test 3 (days 5–6) SS versus water, and Test 4 (days 8–9) fructose versus SS. The mice were given water only on day 7 prior to Test 4 to make it comparable to Test 1, which was preceded by water only access. After 2 days of water only, a second series of 4 tests was conducted as above but with glucose instead of fructose. Next a third series of glucose and SS tests was conducted while the animals were food restricted; the rationale for this series is described below. The mice were given restricted food rations for a week that maintained them at 90% of their ad libitum body weight. While on these limited rations, they were given the following tests: Test 1 (days 1–2) glucose versus water, Test 2 (days 3–4) SS versus water, Test 3 (days 6–7) glucose versus SS. Water only was available on day 5. In all series, the left–right positions of the sweeteners and/or water bottles were switched from the first to second day of each test.

Daily solution intakes were averaged over the 2 days of each test and sweetener preferences were expressed as percent solution intakes. Intakes and preference data were analyzed with ANOVAs. One ANOVA included results from Tests 1 and 4 and asked whether relative intakes of sugar and SS changed across the 2 tests. A second ANOVA included results from Tests 2 and 3 and compared the preference for each sweetener over water. Additional statistical tests are described below.

Results and discussion

In the first test series (Figure 2), the CAST mice consumed significantly more SS than fructose in both Tests 1 and 4 [F(1, 8) = 193.8, P < 0.001]; their SS intake declined slightly from the first to last test while their fructose intakes remained low and unchanged [solution × test, F(1, 8) = 8.4, P < 0.05] as did their percent fructose intakes. In Tests 2 and 3, the CAST mice consumed substantially more sweetener than water [F(1, 8) = 362.3, P < 0.001] and more SS than fructose [solution × test, F(1, 8) = 24.2, P < 0.01]. In contrast to the strong SS preference over fructose displayed by CAST mice in Tests 1 and 4, the B6 mice were indifferent to the sweeteners in these tests although they showed a slight, but nonsignificant increase in their SS preference in Test 4. In Tests 2 and 3, they consumed significantly more sweetener than water [F(1, 8) = 277.7, P < 0.001]; and their fructose and SS intakes did not differ. Compared to the CAST mice, the B6 mice overall consumed less sweetener in Tests 1 and 4 [F(1, 17) = 64.3, P < 0.001], although they consumed more fructose and less SS than did the CAST mice [group × solution, F(1, 17) = 68.1, P < 0.001]. In Tests 2 and 3, the B6 mice consumed less fructose and SS than did the CAST mice [F(1, 17) = 21.3, P < 0.01].

Figure 2.

Figure 2.

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Experiment 2, Test series 1. Mean intakes (+SEM) of 8% fructose, 0.1% sucralose + 0.1% saccharin (SS), and water in 2-day, 2-bottle tests in CAST (left panel) and B6 mice (right panel). (Order of testing is from left to right in the panels.) In Tests 1 and 4, the mice were given the choice of fructose versus SS. In Test 2, the choice was fructose versus water and in Test 3, it was SS versus water. Numbers atop bars represent mean percent preference for that solution. Significant (P < 0.05) intake differences within the 2-bottle tests are indicated by an asterisk (*).

In the second test series (Figure 3), the CAST mice consumed more SS than glucose in Tests 1 and 4 [F(1, 8) = 39.3, P < 0.001] although their SS intake declined and glucose intake increased from the first to last test [solution × test, F(1, 8) = 35.1, P < 0.001]. Percent SS intake also declined from Test 1 to 4 [82–69%, t(8) = 5.4, P < 0.001]. The percent intakes of SS relative to glucose were less pronounced than those for SS relative to fructose in the first series averaged over Tests 1 and 4 [90% vs. 76%, F(1, 8) = 17.2, P < 0.01]. In Tests 2 and 3, the CAST mice consumed substantially more SS and glucose than water and their sweetener intakes did not differ [F(1, 8) = 450.5, P < 0.001]. In contrast, the B6 mice consumed substantially more glucose than SS in Tests 1 and 4 [F(1, 9) = 169.9, P < 0.001] and their glucose intake increased and SS decreased from the first to last test [F(1, 9) = 10.9, P < 0.001]. Their percent intakes of glucose relative to SS were much greater than their percent intakes of fructose relative to SS in the first series [94% vs. 48%, F(1, 9) = 71.2, P < 0.001]. In Tests 2 and 3, the B6 mice consumed substantially more of both sweeteners than water [F(1, 9) = 311.1, P < 0.001] and they drank significantly more glucose than SS [solution × test, F(1, 9) = 134.9, P < 0.001]. The CAST and B6 mice did not differ in their overall sweetener intakes in Tests 1 and 4, but the CAST mice consumed more SS and less glucose than did the B6 mice [F(1, 17) = 169.9, P < 0.001]. Similarly, the CAST mice consumed more SS and less glucose in the sweetener versus water Tests 2 and 3 [F(1, 17) = 61.5, P < 0.001]. In the sugar versus water tests conducted in series 1 and 2, the CAST and B6 mice consumed more glucose than fructose [F(1, 17) = 77.3, P < 0.001], and B6 mice consumed more glucose than the CAST mice, while the fructose intakes of the 2 strains were similar [strain × sugar, F(1, 17) = 18.6, P < 0.001].

Figure 3.

Figure 3.

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Experiment 2, Test series 2. Mean intakes (+SEM) of 8% glucose, 0.1% sucralose + 0.1% saccharin (SS), and water in 2-day, 2-bottle tests in CAST (left panel) and B6 mice (right panel) maintained on ad libitum food. (Order of testing is from left to right in the panels.) In Tests 1 and 4, the mice were given the choice of glucose versus SS. In Test 2, the choice was glucose versus water and in Test 3, it was SS versus water. Numbers atop bars represent mean percent preference for that solution. Significant (P < 0.05) intake differences within the 2-bottle tests are indicated by an asterisk (*).

Because the CAST mice increased their percent glucose intake from Test 1 to 4 in the second test series, a third series was conducted to determine if the mice would come to prefer the glucose to SS with further experience. In particular, the mice were food-restricted to enhance the nutritive value of sugar and given glucose versus water, SS versus water, and then glucose versus SS tests, in that order. As shown in Figure 4, the CAST mice consumed similar amounts of glucose and SS in Tests 1 and 2 but then drank significantly more SS than glucose in Test 3 [t(8) = 8.4, P < 0.001]. Their SS preference of 70% was similar to their 69% SS preference in the last test of series 2 when the animals were not food restricted. Preferences of the B6 mice in the third series were similar to those in the second series, although overall the B6 mice consumed more glucose and SS when food restricted.

Figure 4.

Figure 4.

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Experiment 2, Test series 3. Mean intakes (+SEM) of 8% glucose, 0.1% sucralose + 0.1% saccharin (SS), and water in 2-day, 2-bottle tests in CAST (left panel) and B6 mice (right panel) maintained on restricted food rations. (Order of testing is from left to right in the panels.) In Test 1, the choice was glucose versus water, in Test 2, it was SS versus water, and in Test 3, it was glucose versus SS. Numbers atop bars represent mean percent preference for that solution. Significant (P < 0.05) intake differences within the 2-bottle tests are indicated by an asterisk (*).

Given the preference for fructose over glucose the CAST mice displayed in Test 4 of Experiment 1, we predicted that fructose had stronger postoral reinforcing actions than glucose as well as compared to the non-nutritive SS sweetener. Contrary to this prediction, the CAST mice strongly preferred the non-nutritive SS to fructose as well as to glucose. Consistent with prior findings, the B6 mice strongly preferred glucose to SS. They did not, however, prefer SS to fructose as we observed in our earlier studies (Sclafani et al. 2015, 2016a). This discrepancy can be attributed to the fact that the mice in the earlier studies were naïve to sugars and SS prior to their fructose versus SS choice test series while the present mice had experience with fructose and glucose in Experiment 1. Prior experience with glucose increases the subsequent preference for fructose in B6 mice, which could explain why the sugar-experienced B6 mice in the present experiment did not drink more SS than fructose as did sweetener-naïve mice (Zukerman et al. 2013b).

Experiment 3: Flavor preferences conditioned by intragastric sugar infusions in CAST and B6 mice

The failure of CAST mice to develop preferences for fructose or glucose over the non-nutritive SS solution suggests that both sugars have weak or no postoral appetite-stimulating effects in this strain. Experiment 3 directly evaluated postoral sugar appetition by having CAST mice self-infuse fructose or glucose IG as they drank distinctively flavored (CS+) non-nutritive solutions by mouth; a different flavored solution (CS−) was paired with self-infusions of water. B6 mice were similarly trained and tested to confirm prior findings that the mice of this strain acquire strong preferences for a flavor paired with IG glucose but not for a flavor paired with IG fructose (Sclafani and Ackroff 2012a; Zukerman et al. 2013a).

Materials and methods

Animals

Adult male CAST (n = 9) and B6 mice (n = 10) from Jackson Laboratories were first used in a study of 24 h fat (intralipid) versus water preferences to be reported elsewhere. They were then surgically fitted with chronic gastric catheters while anesthetized with isoflurane (2%) inhalation as previously described (Sclafani et al. 2010). Analgesia was provided by a subcutaneous injection of Buprenorphine SR (1 mg/kg, ZooPharm) at the time of surgery. Two weeks after surgery, the animals were briefly (5 min) anesthetized with isoflurane and fitted with a harness and spring tether (CIH62; Instech Laboratories). The mice had ad libitum access to chow (5001, PMI Nutrition International) and water except where noted.

Apparatus

IG infusion training was conducted in plastic test cages (Sclafani et al. 2010). The sipper spouts were connected to electronic lickometers and a computer that operated syringe pumps which infused fluid into the gastric catheters as the animals licked the CS solutions; the oral-to-infusion intake ratio was maintained at ~1:1. The pump rate was nominally 0.5 mL/min, but the overall infusion rate and volume was controlled by the animal’s licking behavior. Daily oral fluid intakes were measured to the nearest 0.1 g, and IG infusions were recorded to the nearest 0.5 mL.

Test solutions

In Part 1, the CS solutions contained 0.2% (w/w) saccharin and were flavored with 0.05% (w/w) cherry or grape Kool-Aid flavor mix (Kraft Foods). The IG infusates were water and 16% (w/w) glucose. For half the mice, cherry-saccharin was the CS+G paired with IG glucose infusion and grape-saccharin was the CS− paired with water infusion; the flavor-infusate pairs were reversed for the remaining animals. The orally consumed CS+G mixed with the IG sugar infusion in the stomach so that the sugar concentration in the gut was 8%. In Part 2, the CS solutions contained 0.2% saccharin flavored with 0.05% orange or lemon-lime Kool-Aid flavor mix. The CS+F was paired with IG 16% fructose and the CS− was paired with IG water. The flavor-infusate pairs were counterbalanced as in Part 1. In Part 3, the same glucose-paired CS+G and fructose-paired CS+F solutions were used as in Parts 1 and 2.

Procedure

Twenty days after surgery the mice were adapted to infusion cages with ad libitum access to food and water. For 2 days intake of water was paired with IG water infusions. In Part 1, the mice were trained with the CS− paired with IG water infusions (days 1, 3, and 5) and CS+G paired with IG glucose infusions (days 2, 4, and 6) in 23 h/day training sessions. The mice were then given a 2-bottle choice test (days 7 and 8) with the CS+G and CS− solutions paired with their appropriate infusions. The left-right position of the CS+G and CS− solutions was varied using an LRRLLR pattern during training and a LR pattern during testing. Part 2. The mice were given unflavored saccharin paired with IG water for 1 day. They were then trained and tested as in Part 1 except that the CS+F solution was paired with IG infusions of fructose. In Part 3, the mice were retrained with the CS+G (days 1 and 3) and CS+F (days 2 and 4) paired with IG infusions of glucose and fructose, respectively. They were then given a 2-bottle choice test (days 5 and 6) with CS+G versus CS+F for 2 days with the CS solutions paired with their appropriate IG sugar infusions.

CS+ and CS− total intakes (oral + IG) were averaged over 3- and 2-day blocks during training and 2-day blocks during testing analyzed in separate ANOVAs.

Results and discussion

Part 1

During 1-bottle training the CAST mice consumed less (P < 0.05) CS+G than CS− whereas the B6 mice consumed more (P < 0.05) CS+ than CS− [Figure 5; group × CS, F(1, 17) = 21.7, P < 0.001]. In addition, the CS+G training intake of the B6 mice exceeded (P < 0.05) that of the CAST mice; CS− intakes did not differ. In the 2-bottle choice test, both groups consumed more CS+G then CS− but the difference was greater in the B6 mice than in the CAST mice [group × CS, F(1, 17) = 32.0, P < 0.001]. In addition, the percent CS+G intake of the B6 mice exceeded that of the CAST mice [93% vs. 70%, t(17) = 5.2, P < 0.001].

Figure 5.

Figure 5.

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Experiment 3. Mean total oral and IG intakes (+SEM) of the conditioned stimulus (CS+G) paired with IG infusion of 16% glucose, (CS+F) paired with IG 16% fructose, and (CS−) paired IG water during 1-bottle training sessions (train) and 2-bottle test sessions. Data from CAST and B6 mice are presented in the upper and lower panels, respectively. In Part 1, the mice were trained 3 days each with the CS+G and CS− and then given a 2 day, 2-bottle test with CS+G versus CS− (left panels). In Part 2, they were trained 3 days each with the CS+F and CS− and then given a 2-day, 2-bottle test with CS+F versus CS− (middle panels). In Part 3, they were trained 2 days each with the CS+G and CS+F and then given a 2-bottle test with the CS+G versus CS+F (right panels). Numbers atop bars represent mean percent preference for that solution. Significant (P < 0.05) intake differences in the training and 2-bottle tests are indicated by an asterisk (*).

Part 2

During 1-bottle training the CAST and B6 mice did not differ significantly in their CS+F and CS− intakes; overall, the mice consumed somewhat less CS+F than CS− [F(1, 17) = 4.2, P < 0.06]. In the 2-bottle choice test, the CAST mice consumed more (P < 0.001) CS+F than CS− whereas the CS intakes did not differ significantly in the B6 mice [group × CS, F(1, 17) = 5.6, P < 0.05]. The percent CS+F intake of the CAST mice exceeded that of the B6 mice [76% vs. 59%, t(17) = 2.8, P < 0.05]. The CS+G and CS+F percent intakes of the CAST mice in Parts 1 and 2 did not significantly differ (70% vs. 76%) whereas the percent CS+G intake of the B6 mice exceeded that of their CS+F intake [93% vs. 59%, t(9) = 9.4, P < 0.001].

Part 3

During 1-bottle training the CAST mice consumed similar amounts of CS+G and CS+F whereas the B6 mice consumed significantly (P < 0.001) more CS+G than CS+F [group × CS, F(1, 17) = 59.5, P < 0.001]. In addition, the B6 mice consumed more (P < 0.001) CS+G and less (P < 0.05) CS+F than did the CAST mice. In the 2-bottle test, the B6 mice consumed more (P < 0.01) CS+G than CS+F whereas the CAST mice did not significantly differ in their CS+G and CS+F intakes [group × CS, F(1, 17) = 10.3, P < 0.01]. In addition, the CS+G preference was significantly greater in B6 mice than CAST mice [86% vs. 65%, t(17) = 3.1, P < 0.01].

These data revealed that glucose and fructose both have moderate postoral reinforcing actions in CAST mice. IG fructose conditioned a slightly stronger CS+ flavor preference, relative to the CS−, than did IG glucose but the difference was not significant. In the direct choice test, the CAST mice displayed a slight but nonsignificant preference for CS+G over CS+F. In contrast, the B6 mice strongly preferred the CS+G to water and to the CS+F, and failed to prefer the CS+F to CS−, which confirms prior studies (Sclafani and Ackroff 2012a; Zukerman et al. 2013a).

General discussion

The present findings revealed profound differences in the oral- and postoral-based preferences of CAST and B6 mice for glucose and fructose. First, when given the choice between 8% glucose versus fructose, CAST mice developed a 72% preference for fructose while B6 mice displayed a 95% preference for glucose. Second, CAST mice significantly and persistently preferred a non-nutritive sucralose + saccharin solution to glucose and fructose, whereas B6 mice strongly preferred glucose, but not fructose to SS. Third, CAST mice acquired significant, albeit moderate, preferences for CS+G and CS+F flavors paired with IG glucose and fructose, whereas B6 mice acquired a strong preference for the glucose-paired CS+G but not for the fructose-paired CS+F flavor. Fourth, CAST mice, unlike B6 mice, did not significantly prefer the glucose-paired CS+G over the fructose-paired CS+F in a direct choice test.

Sugar preferences are influenced by the sweet taste and postoral actions of the nutrient. The naïve CAST and B6 mice initially equally preferred the glucose and fructose solutions on the first day of Test 1 (Experiment 1) which suggests that the 2 sugars were comparable in taste palatability at the 8% concentration, although postoral factors may have influenced the 24-h intakes. Consistent with this interpretation, B6 mice show equal preferences for the 2 sugars in 1-min choice tests, which minimize postoral influences (Sclafani et al. 2015). Comparable data have not been published with CAST mice although Poole et al. (2016) reported that CAST and B6 mice displayed comparable brief-access lick rates for 8% sucrose. In contrast to the day 1 preference data, B6 mice developed a significant glucose preference (79%) by day 2 of the test which increased to 95% by Test 4 after the separate sweetener versus water Tests 2 and 3. The CAST mice, on the other hand, developed a significant preference (72%) for fructose by Test 4. These delayed, experience-related sugar preferences suggested the influence of postoral sugar effects, which were investigated in Experiment 2 and 3.

Prior studies indicated that a 0.1% sucralose + 0.1% saccharin mixture is highly preferred to 8% glucose and fructose in 1-min and initial 2-day choice tests by B6 and FVB mice (Sclafani et al. 2014, 2015). However, B6 mice rapidly develop a strong preference for glucose but not for fructose over SS (Sclafani et al. 2015, 2016a). This is consistent with flavor conditioning actions of IG glucose but not fructose infusions in this strain (Sclafani and Ackroff 2012a; Zukerman et al. 2013a). In contrast, FVB mice develop preferences for glucose and, to a lesser extent, fructose over SS after separate sweetener versus water tests (Sclafani et al. 2014). This is consistent with their acquired preferences for a CS+G flavor paired with IG glucose and, to a lesser extent, for a CS+F flavor paired with IG fructose (Sclafani et al. 2014). Finally, in 2-day choice tests with 8% glucose versus fructose, both B6 and FVB mice displayed >90% preferences for glucose (Sclafani et al. 2014). In view of these earlier findings, the fructose over glucose preference displayed by the CAST mice in the first experiment led to the prediction that CAST mice, unlike B6 and FVB mice, would more strongly prefer fructose rather than glucose over the non-nutritive SS. Instead, CAST mice significantly preferred SS to both fructose and glucose. Even when food-restricted they drank more SS than glucose in a direct choice test. These results suggested that CAST mice are insensitive to the postoral appetite-stimulating actions of both sugars.

Experiment 3 investigated this possibility using the IG flavor conditioning procedure. CAST mice acquired significant, albeit moderate preferences (70–76%) for CS+G and CS+F flavors paired with IG glucose and IG fructose infusions, respectively, and did not prefer one flavor over the other in a direct choice test. Despite these sugar-conditioned preferences, the CAST mice did not consume more CS+ than CS− during 1-bottle training and, in fact, drank significantly less CS+G than CS− during training. In contrast, B6 mice drank more CS+G than CS− during training and displayed a 93% CS+G preference in the subsequent choice test. On the other hand, they were indifferent to the CS+F flavor during training and testing and strongly preferred the CS+G to the CS+F in the direct choice test. These findings confirm and extend prior data obtained with B6 mice (Sclafani and Ackroff 2012a; Zukerman et al. 2013a). Unlike B6 mice, FVB mice learned to prefer both CS+G and CS+F flavors paired with IG glucose and fructose infusions and consumed more CS+G and CS+F than CS− during 1-bottle training (Sclafani et al. 2014). However, like B6 mice, their CS+G preference was greater than their CS+F preference (98% vs. 80%) (Sclafani et al. 2014).

Given the results of Experiment 3 showing that both fructose and glucose have postoral reinforcing actions in CAST mice, the failure of these mice to develop a preference for these sugars over the non-nutritive SS solution in the second experiment is surprising. Conceivably, sucralose and saccharin may have postoral reinforcing effects via their action on gut sweet receptors, but there is no evidence that non-nutritive sweeteners have postoral appetite-stimulating effects (Ramirez 1994; de Araujo et al. 2008; Sclafani et al. 2010; Tsurugizawa and Uneyama 2014). Instead it appears that the attraction of CAST mice to the sweet taste of the SS mixture outweighs the moderate nutritive conditioning effects of the sugars in this strain.

The comparable conditioning actions of IG fructose and glucose in CAST mice indicate that their preference for fructose over glucose in the first experiment was due to the oral rather than the postoral actions of the sugars. As noted in the introduction, CAST mice differ from B6 mice in showing only a weak preference for maltodextrin, and this might be related to the different fructose versus glucose preferences displayed by the 2 strains. Early rat studies indicated that maltodextrin preference is mediated by a glucose polymer taste receptor distinct from the sweet receptor that responds to sugars and non-nutritive sweeteners (Sclafani 1987). This was indicated by the finding that taste aversions to maltodextrin poorly generalized to sucrose, fructose, and saccharin (Nissenbaum and Sclafani 1987a). However, they generalized to glucose and maltose (a glucose + glucose disaccharide) suggesting that these sugars are ligands for the maltodextrin receptor as well for the sweet receptor. It may be, therefore, that the oral attraction rodents have for glucose (and maltose) is due to a mixture of sweet and maltodextrin tastes, whereas their attraction to fructose is due only to its sweet taste (Sclafani 1987; Ramirez 1996). According to this view, CAST mice may be less attracted to the taste of glucose than B6 mice because they have a less sensitive maltodextrin taste receptor (Poole et al. 2016). Recent studies also suggest that mice have a glucose-selective taste receptor independent of the T1r2/T1r3 sweet receptor (Glendinning et al. 2015; Schier and Spector 2016; Sukumaran et al. 2016) and it is possible that CAST and B6 mice differ in the sensitivity of this glucose-selective receptor. A problem with these interpretations, however, is that naïve CAST mice equally preferred glucose and fructose (Test 1, Experiment 1) and only after separate experience with the 2 sugars did they display a fructose preference (Test 4). This experience-related preference suggests an alternative hypothesis. That is, fructose taste may be more readily associated with postoral sugar actions than is glucose taste in CAST mice. As a result, during the sugar versus water tests CAST mice may acquire a stronger attraction to fructose than to glucose as they associate the tastes of the sugars with their postoral actions. This could be tested by comparing the effectiveness of dilute glucose and fructose solutions to serve as CS+ flavors paired with IG sucrose infusions (sucrose is proposed because it is digested to both glucose and fructose).

Another unresolved question is why, in the sugar versus water tests of Experiments 1 and 2, CAST mice consumed more glucose than fructose. This cannot be attributed to glucose having a more attractive taste, since naïve CAST mice equally preferred glucose and fructose, nor to glucose having a more potent postoral appetition effect, since IG glucose and fructose conditioned comparable CS+ preferences. Furthermore, during 1-bottle training CAST mice consumed comparable amounts of the CS+G and CS+F paired with IG infusions of glucose and fructose, respectively, indicating that the postoral actions of glucose are not less satiating than those of fructose. Conceivably, the oral taste of glucose may be less satiating than that of fructose in CAST mice; see (Mook et al. 1980; Nissenbaum and Sclafani 1987b; Swithers and Hall 1994) for a discussion of oral satiation or habituation. An analysis of drinking bout size and number may give insights into why CAST mice drink more glucose than fructose in sugar versus water tests.

The finding that CAST mice developed a preference for fructose over glucose is novel given the glucose preferences observed with other rodents (B6, FVB, SWR, and BALB mice, and Sprague-Dawley, Long-Evans, and Wistar rats) (Ackroff and Sclafani 1991a, 1991b; Ramirez 1996; Ackroff et al. 1997; Flaherty and Mitchell 1999; Tonosaki 2010; Sclafani et al. 2014, 2015; Wakabayashi et al. 2016). The failure of CAST mice to develop a preference for glucose over a non-nutritive sweetener is also a new finding. In prior studies, rodents acquired preferences for glucose over equally or more-preferred non-nutritive sweeteners (B6, FVB, and SWR mice, Sprague-Dawley and Long-Evans rats) (Ackroff and Sclafani 1991a; Warwick and Weingarten 1994; Sclafani et al. 2014, 2015, 2016a; Kraft et al. 2016). Particularly noteworthy is the finding that CAST mice did not prefer glucose to SS even when food restricted and in energy deficit. Even the fly learns to prefer sugar to a non-nutritive sweetener (Dus et al. 2011). CAST mice learned to prefer flavored solutions paired with IG glucose and fructose, so why don’t they learn to prefer the sugars to SS? The genetic origin of CAST mice (Mus musculus castaneus) differs from B6 and other common inbred mouse strains (Mus musculus domesticus) (Davis et al. 2007) which may account for their unusual sweetener preferences. Further comparative studies of CAST and other mouse strains may reveal the genetic mechanisms responsible for acquired sugar preferences. Finally, limitations of the current study are acknowledged, including the use of only a single sugar concentration (8%) and the presentation of the sugars in a fixed rather than a counterbalanced order.

Funding

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [DK-31135].

Acknowledgment

We thank Kwame McCartney and Martin Zartarian for their technical assistance.

References

  1. Ackroff K, Sclafani A. 1991a. Flavor preferences conditioned by sugars: rats learn to prefer glucose over fructose. Physiol Behav. 50:815–824. [DOI] [PubMed] [Google Scholar]
  2. Ackroff K, Sclafani A. 1991b. Sucrose to polycose preference shifts in rats: the role of taste, osmolality and the fructose moiety. Physiol Behav. 49:1047–1060. [DOI] [PubMed] [Google Scholar]
  3. Ackroff K, Sclafani A, Axen KV. 1997. Diabetic rats prefer glucose-paired flavors over fructose-paired flavors. Appetite. 28:73–83. [DOI] [PubMed] [Google Scholar]
  4. Bachmanov AA, Bosak NP, Lin C, Matsumoto I, Ohmoto M, Reed DR, Nelson TM. 2014. Genetics of taste receptors. Curr Pharm Des. 20:2669–2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis RC, Jin A, Rosales M, Yu S, Xia X, Ranola K, Schadt EE, Lusis AJ. 2007. A genome-wide set of congenic mouse strains derived from CAST/Ei on a C57BL/6 background. Genomics. 90:306–313. [DOI] [PubMed] [Google Scholar]
  6. de Araujo IE, Oliveira-Maia AJ, Sotnikova TD, Gainetdinov RR, Caron MG, Nicolelis MAL, Simon SA. 2008. Food reward in the absence of taste receptor signaling. Neuron. 57:930–941. [DOI] [PubMed] [Google Scholar]
  7. Dus M, Min SH, Keene AC, Lee GY, Suh GSB. 2011. Taste-independent detection of the caloric content of sugar in Drosophila. Proc Natl Acad Sci U S A. 108:11644–11649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Flaherty CF, Mitchell C. 1999. Absolute and relative rewarding properties of fructose, glucose, and saccharin mixtures as reflected in anticipatory contrast. Physiol Behav. 66:841–853. [DOI] [PubMed] [Google Scholar]
  9. Glendinning JI, Stano S, Holter M, Azenkot T, Goldman O, Margolskee RF, Vasselli JR, Sclafani A. 2015. Sugar-induced cephalic-phase insulin release is mediated by a T1r2 + T1r3-independent taste transduction pathway in mice. Am J Physiol Regul Integr Comp Physiol. 309:R552–R560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kraft TT, Huang D, Lolier M, Warshaw D, LaMagna S, Natanova E, Sclafani A, Bodnar RJ. 2016. BALB/c and SWR inbred mice differ in post-oral fructose appetition as revealed by sugar versus non-nutritive sweetener tests. Physiol Behav. 153:64–69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mook DG, Bryner CA, Rainey LD, Wall CL. 1980. Release of feeding by the sweet taste in rats: oropharyngeal satiety. Appetite. 1:299–315. [Google Scholar]
  12. Nissenbaum JW, Sclafani A. 1987a. Qualitative differences in polysaccharide and sugar tastes in the rat: a two-carbohydrate taste model. Neurosci Biobehav Rev. 11:187–196. [DOI] [PubMed] [Google Scholar]
  13. Nissenbaum JW, Sclafani A. 1987b. Sham-feeding response of rats to polycose and sucrose. Neurosci Biobehav Rev. 11:215–222. [DOI] [PubMed] [Google Scholar]
  14. Poole RL, Aleman TR, Ellis HT, Tordoff MG. 2016. Maltodextrin acceptance and preference in eight mouse strains. Chem Senses. 41:45–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ramirez I. 1994. Stimulation of fluid intake by carbohydrates: interaction between taste and calories. Am J Physiol Regul Integr Comp Physiol. 266:R682–R687. [DOI] [PubMed] [Google Scholar]
  16. Ramirez I. 1996. Is fructose sweeter than glucose for rats? Physiol Behav. 60:1299–1306. [DOI] [PubMed] [Google Scholar]
  17. Reed DR, Li S, Li X, Huang L, Tordoff MG, Starling-Roney R, Taniguchi K, West DB, Ohmen JD, Beauchamp GK, et al. 2004. Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains. J Neurosci. 24:938–946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schier LA, Spector AC. 2016. Behavioral evidence for more than one taste signaling pathway for sugars in rats. J Neurosci. 36:113–124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sclafani A. 1987. Carbohydrate taste, appetite, and obesity: an overview. Neurosci Biobehav Rev. 11:131–153. [PubMed] [Google Scholar]
  20. Sclafani A. 2013. Gut-brain nutrient signaling. Appetition vs. satiation. Appetite. 71:454–458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sclafani A, Ackroff K. 2012a. Flavor preferences conditioned by intragastric glucose but not fructose or galactose in C57BL/6J mice. Physiol Behav. 106:457–461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sclafani A, Ackroff K. 2012b. Role of gut nutrient sensing in stimulating appetite and conditioning food preferences. Am J Physiol Regul Integr Comp Physiol. 302:R1119–R1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sclafani A, Adamantidis A, Ackroff K. 2016a. MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice. Physiol Behav. 163:239–244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sclafani A, Glass DS, Margolskee RF, Glendinning JI. 2010. Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice. Am J Physiol Regul Integr Comp Physiol. 299:R1643–R1650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sclafani A, Vural AS, Ackroff K. 2016b. Profound taste/nutrient preference differences between CAST/Ei vs. C57BL/6 mice. Chem Senses. 41:e92. [Google Scholar]
  26. Sclafani A, Zukerman S, Ackroff K. 2014. Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition. Am J Physiol Regul Integr Comp Physiol. 307:R1448–R1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sclafani A, Zukerman S, Ackroff K. 2015. Postoral glucose sensing, not caloric content, determines sugar reward in C57BL/6J mice. Chem Senses. 40:245–258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith BK, Andrews PK, West DB. 2000. Macronutrient diet selection in thirteen mouse strains. Am J Physiol. 278:R797–R805. [DOI] [PubMed] [Google Scholar]
  29. Sukumaran SK, Yee KK, Iwata S, Kotha R, Quezada-Calvillo R, Nichols BL, Mohan S, Pinto BM, Shigemura N, Ninomiya Y, et al. 2016. Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides. Proc Natl Acad Sci U S A. 113:6035–6040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Swithers SE, Hall WG. 1994. Does oral experience terminate ingestion? Appetite. 23:113–138. [DOI] [PubMed] [Google Scholar]
  31. Treesukosol Y, Blonde G, Spector AC. 2009. The T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to Polycose: implications for saccharide taste receptors in mice. Am J Physiol Regul Integr Comp Physiol. 296:R855–R865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Treesukosol Y, Smith KR, Spector AC. 2011. Behavioral evidence for a glucose polymer taste receptor that is independent of the T1R2+3 heterodimer in a mouse model. J Neurosci. 31:13527–13534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Treesukosol Y, Spector AC. 2012. Orosensory detection of sucrose, maltose, and glucose is severely impaired in mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal. Am J Physiol Regul Integr Comp Physiol. 303:R218–R235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tonosaki K. 2010. Relationships between cephalic phase insulin release and taste modalities. In: Zafra MA, Molina F, Puerto A, editors. The cephalic/neural phase in nutrition. Kerala (India): Research Signpost; p. 83–92. [Google Scholar]
  35. Tsurugizawa T, Uneyama H. 2014. Differences in BOLD responses to intragastrically infused glucose and saccharin in rats. Chem Senses. 39:683–691. [DOI] [PubMed] [Google Scholar]
  36. Wakabayashi KT, Spekterman L, Kiyatkin EA. 2016. Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose—association with glucose entry into the brain. Eur J Neurosci. 43:1422–1430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Warwick ZS, Weingarten HP. 1994. Dissociation of palatability and calorie effects in learned flavor preferences. Physiol Behav. 55:501–504. [DOI] [PubMed] [Google Scholar]
  38. Zukerman S, Ackroff K, Sclafani A. 2013a. Post-oral appetite stimulation by sugars and nonmetabolizable sugar analogs. Am J Physiol Regul Integr Comp Physiol. 305:R840–R853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zukerman S, Glendinning JI, Margolskee RF, Sclafani A. 2009. T1R3 taste receptor is critical for sucrose but not Polycose taste. Am J Physiol Regul Integr Comp Physiol. 296:R866–R876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zukerman S, Glendinning JI, Margolskee RF, Sclafani A. 2013b. Impact of T1r3 and Trpm5 on carbohydrate preference and acceptance in C57BL/6 mice. Chem Senses. 38:421–437. [DOI] [PMC free article] [PubMed] [Google Scholar]

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