Diabetic Rats Prefer Glucose-paired Flavors over Fructose-paired Flavors

Appetite, 1997, 28, 73–83

Diabetic Rats Prefer Glucose-paired Flavors over

Fructose-paired Flavors

KAREN ACKROFF and ANTHONY SCLAFANIDepartment of Psychology, Brooklyn College and the Graduate School ofNew York City University, U.S.A.

KATHLEEN V. AXENDepartment of Health and Nutrition Sciences, Brooklyn College and theGraduate School, City University of New York, U.S.A.

Prior studies indicate that glucose has a more potent postingestive reinforcingeffect than fructose. The role of insulin in this effect was examined by comparingsugar-conditioned flavor preferences in normal and streptozotocin-diabetic rats.In Experiment 1, diabetic rats, like normal rats, preferred a cue flavor that hadbeen mixed into 8% glucose solution over a flavor mixed with 8% fructose.Both taste and postingestive properties of glucose may have contributed to thispreference. Experiment 2 evaluated postingestive reinforcement by pairing cueflavors with intragastric infusions of glucose and fructose. Both diabetics andnormals acquired a preference for the flavor paired with intragastric 16% glucoseinfusions over the flavor paired with 16% fructose infusions although the preferencewas somewhat smaller in the diabetic rats. Taken together, the results indicatethat a normal insulin secretory response to glucose is not required for glucose-conditioned flavor preferences. The diabetic rats’ reduced flavor preference inExperiment 2 suggests that insulin may play some role in glucose conditioningalthough this may be secondary to alterations in gastrointestinal motility char-acteristic of diabetic animals. 1997 Academic Press Limited

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Recent studies in our laboratory have compared the reinforcing effects of themonosaccharides glucose and fructose. Despite the equal energy value of these twosugars, it has repeatedly been found that rats acquire strong preferences for glucoseover fructose. In comparisons of pairs of isocaloric carbohydrate solutions, ratscome to prefer glucose and glucose-only saccharides (maltose and Polycose) overfructose or a fructose-containing saccharide (sucrose) even though they may initiallyprefer the fructose-containing carbohydrate (Ackroff & Sclafani, 1991b). We have

Correspondence to: A. Sclafani, Department of Psychology, Brooklyn College of CUNY, Brooklyn,NY 11210 U.S.A.

This research was supported by grants from the National Institute of Diabetes and Digestive andKidney Diseases (DK-31135), the Faculty Research Award Program of the City University of New York,and a NIMH Research Scientist Award (MH-00983) to Anthony Sclafani. Kool-Aid was generouslydonated by General Foods.

0195–6663/97/010073+11 $25.00/0/ap960058 1997 Academic Press Limited

74 K. ACKROFF ET AL.

found that rats also learn to prefer a cue flavor (e.g., grape) paired with glucoseover a different flavor (e.g., cherry) paired with fructose solution (Ackroff & Sclafani,1991a). This glucose-reinforced preference is obtained with rats drinking flavoredsugar solutions as well as with rats drinking flavored water paired with intragastric(IG) sugar infusions. These and other results (Sclafani & Ackroff, 1994) indicatethat the postingestive actions of glucose are much more reinforcing than those offructose.

Why glucose and fructose differ in their reinforcing potency is not known. Thesugars are identical in molecular formula and caloric value but have differentmolecular configurations and are metabolized differently. Compared to glucose,fructose leaves the stomach more rapidly but it is absorbed more slowly in theintestines; it is cleared by the liver, leaving virtually no fructose in the peripheralcirculation (Moran & McHugh, 1981; Niewoehner, Gilboe & Nuttall, 1984a; Nie-woehner, Gilboe, Nuttall & Nuttall, 1984b; Van den Berghe, 1978). Another majordifference between the two sugars is that glucose, unlike fructose, produces a rapidrelease of insulin (Kneepkens, 1989; Rodin, Reed & Jamner, 1988). This differentialeffect on insulin release suggests the possibility that insulin mediates carbohydrate-conditioned flavor preferences. In support of this notion, Oetting reported that sham-feeding rats acquired a preference for a flavored milk paired with insulin injectionover a different flavored milk paired with saline injection (Oetting & VanderWeele,1985). However, in a subsequent experiment from the same laboratory, real-feedingrats were observed to avoid the insulin-paired flavored milk (VanderWeele, Deems& Kanarek, 1990). The latter finding was attributed to potential aversive effects ofinsulin, such as faster gastric emptying, that are not important in the sham-feedingpreparation.

The role of insulin in flavor preference learning can also be studied usinghypoinsulinemic diabetic rats. Tordoff, Tepper and Friedman (1987) reported thatdiabetic rats, unlike controls, develop a preference for a flavor paired with corn oilover a flavor paired with an isocaloric glucose solution. They interpreted this resultas evidence for the idea that fuel utilization is the basis for the reinforcing effect ofnutrients. According to their view, diabetic rats do not learn to prefer glucose orglucose-paired flavors because of their impaired ability to utilize this sugar. However,their data are also compatible with the hypothesis that insulin is the signal for thereinforcing effect of glucose.

The present study sought to determine if the enhanced reinforcing effect ofglucose relative to fructose is mediated by insulin. If so, diabetic rats, unlike normalanimals, should not come to prefer flavors paired with glucose over flavors pairedwith fructose. This possibility was investigated using two different flavor preferenceconditioning methods. In the first experiment the rats were trained to drink flavoredglucose and flavored fructose solutions. With this training procedure, preferencesmay be conditioned by both the taste and the postingestive effects of the sugars.The second experiment focused on postingestive conditioning by pairing differentcue flavors with intragastric infusions of glucose and fructose.

E 1

The first experiment used an oral conditioning paradigm to examine the role ofinsulin in reinforcing glucose-based preferences. In previous work, normal rats given

75DIABETICS PREFER GLUCOSE

one-bottle access to flavored glucose and fructose solutions (8% or 32%) subsequentlypreferred the glucose-paired flavor in two-bottle tests (Ackroff & Sclafani, 1991a).Prior to training, nondeprived rats preferred 32% fructose to 32% glucose, butshowed no preference at the 8% concentration (see also Ackroff & Sclafani, 1991b).In the present experiment, therefore, diabetic and control rats were trained withflavored 8% glucose and fructose solutions. Their preferences for these solutions, aswell as for the flavors presented in glucose-fructose mixtures were then determined.

Method

SubjectsAdult female rats were obtained (Charles River Laboratories, Wilmington, MA,

U.S.A.). The animals were 80 days of age and weighed 250 g (range 237–275 g) onthe day of the streptozotocin treatment. Purina Chow (No. 5001 in powder form)and tap water were available ad libitum except during daily 30 min test periods.

ProcedureBaseline food intake, water intake, and body weight were recorded for one week.

The rats were divided into two groups matched for intakes and body weight. Onegroup (n=12) was injected ip with 65 mg/kg streptozotocin (Sigma Chemical, St.Louis, MO, U.S.A.) in citrate buffer (pH 4·5); the control group (n=9) received thesame volume dose of buffer only. Twelve days after the injection, a tail-blood samplewas analysed by the glucose oxidase method following a 3-h fast in the morning.The streptozotocin-treated rats all had plasma glucose values greater than 400 mg/dl and were considered diabetic. The diabetic rats weighed 248·3±6·4 g and thecontrol rats 268·3±6·8 g when testing began on day 14 post-injection.

The rats were initially tested with sugar solutions containing 8% fructose (SigmaChemical) or 8% glucose (BioServ, Frenchtown, NJ, U.S.A.) flavored with 0·05%unsweetened grape or cherry Kool-Aid (General Foods, White Plains, NY, U.S.A.);the solutions were prepared using tap water on a w/v basis. Half the rats in eachgroup received cherry-glucose and grape-fructose; the other half received the oppositeflavor-sugar pairing. The solutions were presented in graduated 50 ml plastic cylindersfitted with rubber stoppers and stainless-steel drinking spouts. In all two-bottle tests,the left-right positions of the bottles were alternated daily to counteract any sidepreferences. The sugar solutions were available 30 min/day in the rats’ home cages;food and water were removed for the session and the subsequent hour.

The rats were given four daily two-bottle choice sessions to determine their initialpreference for the flavored sugar solutions (pre-test). For the next 8 days they weregiven one-bottle training sessions, with the flavored glucose and fructose solutionspresented on alternate days, to provide unambiguous experience with the individualflavor-sugar pairs. This was followed by another two-bottle test (two sessions) withthe flavored sugar solutions (post-test). Finally, the rats were tested for their preferencefor the specific flavors by presenting the cue flavors in mixed sugar solutions; i.e.,they were given two bottles that each contained 4% glucose and 4% fructose, oneflavored with cherry and the other with grape (two sessions; flavor test). Four ofthe diabetic rats and one control rat drank very little during testing and their datawere discarded, leaving final group sizes of eight each. The data from the last twosessions of each test were entered in analyses of variance. All significant differencesbetween means were p<0.05 or less.


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F 1. Experimental 1. Mean (+SE) intakes of flavored glucose and fructose solutionsby diabetic rats (B) and control rats (A). In the two-bottle pre and post tests and one-bottletraining, sugar concentrations were 8%. In the flavor test, both bottles contained 4% of eachsugar. The averages of the last two days of each phase are shown. Φ, 8% glucose + flavor;∆, 8% fructose + flavour; Ρ, G-flavored mixture; Ε, F-flavored mixture.

Results and Discussion

Sugar intakes and preferences (expressed as percent of total intake) during thevarious training and test periods are shown in Fig. 1. In the initial preference test,the control and diabetic groups both consumed more flavored glucose than flavoredfructose (7·1 vs. 3·1 ml, F(1,14)=8·8, p=0·01) and the two groups did not reliablydiffer in their solution intakes. Both groups also consumed more glucose thanfructose during the one-bottle training sessions (13·0 vs. 7·2 ml, F(1,14)=47·9,p<0.0001), and, overall, the diabetic rats consumed more flavored sugar solutionthan did the control group (12·8 vs. 7·4 ml, F(1,14)=11·8, p<0·01). In the post-training choice tests the diabetics continued to consume more solution than thecontrols (16·8 vs. 11·2 ml, F(1,14)=11·8, p<0·01) and both groups consumed moreflavored glucose than flavored fructose (11·9 vs. 2·1 ml, F(1,14)=46·0, p<0·0001).The animals consumed more flavored glucose in the post-training choice test than


in the initial test (F(1,14)=11·3, p<0·005) while their flavored fructose intake remainedabout the same. When tested with the flavored mixed-sugar solutions, both groupsstrongly preferred (88–91%) the solution with the flavor previously paired withglucose (F(1,14)=49·3, p<0·0001). Overall, the diabetic rats consumed more flavoredmixed-sugar solution than the controls (18·8 vs. 10·6 ml, F(1,14)=13·0, p<0·01).

These results demonstrate that diabetic rats are like normal animals in theirpreference for a glucose solution over a fructose solution and in their learning toprefer a cue flavor paired with a glucose solution. The magnitude of the conditionedflavor preference was greater than the 77% observed under similar conditions in aprevious study (Ackroff & Sclafani, 1991a). Diabetics differed from controls only intheir greater overall fluid intake in some tests which is consistent with the characteristicpolydipsia of diabetes. The similar sugar preferences displayed by the diabetic andcontrol animals suggest that the reinforcing effect of glucose relative to fructose isnot mediated by glucose-stimulated insulin release.

The glucose preference observed in the initial preference test (pre-test) wasunexpected. In a previous study (Ackroff & Sclafani, 1991a) nondeprived rats showedequal intakes of flavored 8% glucose and fructose solutions under similar testconditions; the reason for the glucose preference in the present study is unknown.One interpretation of the rats’ post-training preference for the glucose-paired flavoris that it reflects flavor-flavor conditioning; that is, the rats learned to prefer the cueflavor that was associated with the more preferred glucose flavor. This possibilitycannot be excluded, but note that in prior studies normal rats developed strongpreferences for glucose-paired flavors whether they preferred glucose or fructose inpre-training choice tests (Ackroff & Sclafani, 1991a). Furthermore, rats learn toprefer a glucose-paired flavor over a fructose-paired flavor even when the sugars areinfused intragastrically and therefore are not tasted (Sclafani, Cardieri, Tucker, Blusk& Ackroff, 1993).

E 2

In the first experiment, both taste and postingestive reinforcing properties of thesugars may have contributed to the conditioned flavor preference. To specificallyevaluate the postingestive reinforcing effects of the two sugars in normal and diabeticrats, the second experiment used an intragastric (IG) conditioning procedure. Withthis method, the rats drank sucrose and saccharin-sweetened cue flavors that werepaired with IG sugar infusions. To prevent differential exposure to the cue flavorsand their paired IG sugar infusions, intakes were limited during the daily trainingsessions.

Methods

SubjectsNew rats similar to those of Experiment 1 were used. The animals were 95 days

of age and weighed 253 g (range 239–291 g) on the day of the streptozotocin treatment.They had ad libitum access to Purina chow meal and water in their home cagesexcept during daily 30 min test periods and as noted.


SolutionsBecause rats will not readily drink unsweetened Kool-Aid flavors, the base

solution for the cue flavors contained 2% sucrose and 0·2% saccharin. The sucrosewas included to increase the palatability over that of plain saccharin, which issometimes avoided by rats. Grape and cherry Kool-Aid were added to the sucrose-saccharin base at 0·5% by weight. The infused glucose and fructose solutions wereprepared at 16% concentrations. Because an equal volume of fluid was consumedorally, the net concentration of glucose and fructose in the stomach was 8% as inExperiment 1.

ApparatusThe rats were trained and tested during daily sessions in plastic test cages in a

quiet room adjacent to the colony. Above each cage, plastic tubing from a syringepump was connected to the input port of a swivel on a counterbalanced lever. Whenthe rats were to be infused, plastic tubing protected by a stainless steel springconnected the swivel’s output port to the rat’s IG catheter (described below). Adrinking tube with a stainless steel spout was mounted on the front wall of the cage.Licking behavior was monitored by an electronic drinkometer and a microcomputer.During training sessions, the rat’s licks activated the syringe pump, which had anominal rate of 1·3 ml/min. The oral intake/infusion ratio was maintained at 1:1 bycomputer software.

ProcedureFor the first two days the rats were pre-exposed to the unflavored base solution,

receiving 30 ml/day presented in their cages. On the second night the water bottleswere removed. Pre-training was conducted for the next 7 days, with 30 min accessto unflavored sucrose-saccharin solution in the test cages. After the third session,the water bottles were returned to the home cages and the rats were maintained onwater ad libitum for the remainder of the study.

After pre-training, the rats were fitted with IG catheters. The catheter was a15 cm length of 0·04-in ID silicone tubing with a bead of Silastic adhesive at the tipand a 2 cm square of Marlex surgical mesh fastened 1 cm from the tip. The stomachwas externalized through a 3-cm incision. A purse-string suture was placed in thefundus of the stomach along the greater curvature and a stab wound was made inthe center. The tip of the catheter was inserted and the suture drawn closed; theSilastic bead served to hold the tip inside the stomach. The Marlex mesh was suturedto the stomach to provide additional anchoring of the catheter. The other end ofthe tube was routed under the skin to the back of the neck and was connected to aLuer-Lok assembly fixed to the skull with dental cement and stainless steel screws.The abdominal and head incisions were closed with sutures. When not in use theLuer-Lok assembly was kept closed with a plastic cap. The animals were given 8–12days to recover from surgery.

The rats were divided into two groups matched for body weight and water intake.The diabetic group (n=13) was injected with streptozotocin as in Experiment 1, andthe control group (n=9) was injected with buffer. Four days later, fasting bloodglucose was measured as in Experiment 1. For the next 3 days the rats were given30 min access to unflavored sucrose-saccharin in the test cages as before. On thebasis of low initial measures of blood glucose, blood glucose was retested in eightrats of the diabetic group. Because they did not show the characteristic blood glucose


elevation, they were given a supplementary dose of 16 mg streptozotocin. Four dayslater blood glucose was again retested, and seven of the eight rats now met the400 mg/dl criterion. In addition, five diabetic rats died and one rat’s catheter failedduring the experiment, leaving a final group of six rats. One control rat died, leavinga final group of eight rats. The diabetic rats weighed 256·3±3·7 g and the controlrats 271·1±5·0 g when testing began one week after the second injection.

For two sessions, the rats drank unflavored sucrose-saccharin and were infusedwith water. The 10-day training period then began. All training sessions lasted 30min. On odd-numbered days, the rats drank cherry sucrose-saccharin, and on even-numbered days they drank grape sucrose-saccharin. Half of the rats in each groupwere infused with glucose when they drank cherry and fructose when they drankgrape. The flavor-infusion pairs were reversed for the remaining rats. The oral andinfusion volumes were each limited to 8 ml. The spouts were presented on the leftand right sides on the cage in an ABBA alternation. Finally, two 30 min sessions ofpreference testing were conducted by offering unlimited access to both solutions.During these tests the rats were not infused intragastrically.

Results and Discussion

Average solution intakes and glucose preferences (expressed as percent of totalintake) for the last two sessions of training and the two sessions of preference testingare shown in Fig. 2. By the end of training, the rats were consuming more of theglucose-paired flavor than of the fructose-paired flavor (6·3 vs. 5·2 ml, F(1,12)=16·0,p<0·002). However, the flavor intakes were different in the two groups, F(1,12)=5·2, p<0·05. The control rats drank similar amounts of the two flavors, and thediabetics’ glucose-paired flavor intake was similar to that of controls. The diabeticsconsumed less fructose- than glucose-paired flavor during training (4·0 vs. 6·0 ml).

In the preference sessions, when intakes were not limited, both the control anddiabetic groups drank more of the glucose-paired flavor than of the fructose-pairedflavor (F(1,12)=59·1, p<0·0001). The groups differed, however, in their intakes ofthe flavors, F(1,12)=9·3, p=0·01. The controls drank more of the glucose-pairedflavor than did the diabetics (11·6 vs. 6·0 ml) and both groups consumed similarsmall amounts of the fructose-paired flavor. The control preference for the glucose-paired flavor was thus greater than that of the diabetics (88% vs. 75%), but bothgroups’ preferences were significant (p<0·05, t-tests). The control group drank moretotal solution than the diabetic group in the preference tests (13·2 vs. 7·6 ml,F(1,12)=9·0, p<0·02).

These data show that diabetic rats develop preferences for a glucose-paired flavorover a fructose-paired flavor even when they do not taste the individual sugarsduring training and testing and do not express polydipsia in the training sessions.The magnitude of the preferences seen in diabetics and controls was in the samerange as that of rats trained and tested in a continuous access (23 h/day) procedurewith chow freely available (Sclafani et al., 1993).

The limits on intake during training were chosen to keep total sugar intake nohigher than the fructose intake of diabetics during training in Experiment 1. Giventhe relatively low intakes in these animals, it appears to have been unnecessary. Apossible explanation for this lower intake is that infused sugars were more satiatingthan consumed sugars, perhaps due to differences in gastric emptying. The controls’increase in intake of glucose-paired flavor from training to testing may reflect both


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F 2. Experiment 2. Mean (+SE) intakes of glucose- and fructose-paired cuesolutions by diabetic rats (B) and control rats (A). During training, intake of the flavoredsolutions (cherry and grape 2% sucrose + 0·2% saccharin) was paired with intragastricisovolemic infusion of 16% glucose or fructose solution. Only one flavor and its associatedinfusion were presented on each training day; the data are the average of the last two daysfor each pair. During the post test, both flavored cue solutions were offered and no intragastricinfusions were given. See text for additional details. Φ, glucose flavor; ∆, fructose flavor.

the conditioned preference and a release from the satiating effect of glucose, whichwas absent during the test. It is not clear why the diabetics did not increase theirintake above training levels. One possibility is that the acceleration of gastric emptyingdue to the diabetic state (Granneman & Stricker, 1984) made the infusions evenmore satiating for diabetics than for normal rats. In addition, the faster gastricemptying of fructose than glucose (Moran & McHugh, 1981) may explain why,during the already-limited training sessions, they consumed less fructose than glucose.The stronger effects of their conditioned satiety responses may have limited theexpression of the conditioned preference in the diabetics.

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In confirmation of our previous experiments (Ackroff & Sclafani, 1991a; Ackroff& Sclafani, 1991b; Sclafani & Ackroff, 1994; Sclafani et al., 1993), the control


animals displayed a strong preference for glucose and the glucose-paired flavor overfructose and the fructose-paired flavor. The new finding here is that diabetic rats,like normal animals, also prefer glucose to fructose, and acquire a preference forthe glucose-paired flavor. This suggests that a normal insulin secretory response maynot be required to mediate the rat’s preference for glucose relative to fructose, orthe reinforcing effect of glucose in producing the conditioned flavor preference. Thiscan be inferred from the persistence of these behaviors in rats showing highlyimpaired control of blood glucose, although their insulin secretory responses havenot been directly assessed. However, the diabetic rats’ smaller preference for theglucose-paired flavor after intragastric training in Experiment 2 suggests that insulinmay support the acquisition of glucose-based preferences under some conditions.

Other studies have also found that diabetic rats avidly consume glucose solutionsdespite their impaired ability to metabolize the sugar (Brief & Davis, 1982; Panksepp& Meeker, 1976; Tepper & Friedman, 1991). Tepper and Friedman (1991) reportedthat diabetic rats readily consumed dilute glucose and fructose solutions in short-term tests; at the 0·4 concentration (close to the 8% concentration used here) thediabetics drank more glucose than fructose in one-bottle tests (and less fructose thannormals). When each sugar was paired with water the diabetic animals expressedsimilar preferences for the two sugars (>70%); glucose vs. fructose preferences werenot assessed. These results are consistent with the present data suggesting that thediabetic state does not eliminate the postingestive reinforcing consequences of glucoserelative to that of fructose. This may occur because the reinforcing signals producedby glucose originate at preabsorptive sites (e.g., intestinal glucoreceptors) and/or atpostabsorptive sites not dependent upon insulin (liver, brain).

As noted above, one hypothesis involving an insulin-independent postabsorptivesite is the suggestion that fuel utilization is the important event in reinforcement bynutrients. Tordoff, Ulrich & Sandler (1990) reported that diabetes enhanced theflavor reinforcing action of an oil emulsion relative to an isocaloric glucose solution.They took this as evidence that nutrient-based conditioning “requires a signal relatedto fuel oxidation rather than to fuel delivery or absorption” (p 486). According totheir fuel oxidation hypothesis, however, diabetic rats should also show a reducedpreference for glucose-paired flavors relative to fructose-paired flavors because thefructose would provide proportionately more fuel for the liver. The present findingsdo not support the idea that fuel oxidation is the critical event mediating nutrient-conditioned flavor preferences but suggest instead that it may contribute along withother postingestive processes (e.g., preabsorptive nutrient detection) in reinforcingthe food choices of animals.

The streptozotocin treatment used to produce the diabetic state has widespreadeffects, creating an animal that loses weight and is effectively energy deprived whenmaintained on carbohydrate-rich chow. It could be argued, therefore, that food-restricted rather than ad libitum fed, intact rats are a more appropriate control fordiabetic rats in feeding studies. Food deprivation, however, does not fundamentallyalter flavor preference conditioning by glucose. In a prior study using the oralconditioning procedure of Experiment 1, both ad libitum and food-restricted intactrats developed strong preferences for a glucose-paired flavor over a fructose-pairedflavor (Ackroff & Sclafani, 1991a). Comparable data using the IG conditioningmethods of Experiment 2 are not available. However, we have previously reportedthat IG glucose infusions produce much stronger flavor preferences than do IG


fructose infusions in normal rats trained 23 hr/day with food ad libitum or trained2 hr/day while food-restricted (Sclafani et al., 1993).

The present results along with prior work in this laboratory show that ratsrapidly learn to prefer glucose-paired flavors over fructose-paired flavors whetherthe flavors are mixed into the sugar solutions (providing oral contact with the sugars)or paired with IG sugar infusions (Ackroff & Sclafani, 1991a; Sclafani et al., 1993).Tordoff et al. (1990) reported contrary results with sugar solutions paired withflavored chow but we failed to replicate their findings (Ackroff & Sclafani, 1991a).Each sugar will reinforce a preference for a flavor paired with it over a flavor pairedwith a nonnutritive alternative (Ackroff & Sclafani, 1991a; Sclafani & Ackroff, 1994;Tordoff et al., 1987; Tordoff et al., 1990), but only glucose reinforces preference fora flavor that precedes it by a short (10 min) delay (Sclafani & Ackroff, 1994). Whenthe contribution of the sugars’ flavor is removed, glucose supports strong preferencesrelative to nonnutritive infusions, but at best rats show only weak preferences forflavors paired with IG fructose infusions (Sclafani et al., 1993). Taken together, thesefindings indicate that both sugars have palatable tastes that can reinforce preferencesvia flavor-flavor conditioning (see Sclafani & Ackroff, 1994), but only glucose has apotent postingestive reinforcing effect. The identity and site of the glucose reinforcingsignal awaits further investigation.

xdR

Ackroff, K. & Sclafani, A. (1991a). Flavor preferences conditioned by sugars: Rats learn toprefer glucose over fructose. Physiology and Behavior, 50, 815–824.

Ackroff, K. & Sclafani, A. (1991b). Sucrose to Polycose preference shifts in rats: The role oftaste, osmolality, and the fructose moiety. Physiology and Behavior, 49, 1049–1060.

Brief, D. J. & Davis, J. D. (1982). Diabetes enhances the palatability of glycerol and glucose.Physiology and Behavior, 29, 561–566.

Granneman, J. G. & Stricker, E. M. (1984). Food intake and gastric emptying in rats withstreptozotocin-induced diabetes. American Journal of Physiology, 247, R1054–R1061.

Kneepkens, C. M. F. (1989). What happens to fructose in the gut? Scandinavian Journal ofGastroenterology, 24 (Suppl. 171), 1–8.

Moran, T. H. & McHugh, P. R. (1981). Distinctions among three sugars in their effects ongastric emptying and satiety. American Journal of Physiology, 241, R25–R30.

Niewoehner, C. B., Gilboe, D. P. & Nuttall, F. Q. (1984a). Metabolic effects of oral glucosein the liver of fasted rats. American Journal of Physiology, 246, E89–E94.

Niewoehner, C. B., Gilboe, D. P., Nuttall, G. A. & Nuttall, F. Q. (1984b). Metabolic effectsof oral fructose in the liver of fasted rats. American Journal of Physiology, 247, E505–E512.

Oetting, R. L. & VanderWeele, D. A. (1985). Insulin suppresses intake without inducing illnessin sham feeding rats. Physiology and Behavior, 34, 557–562.

Panksepp, J. & Meeker, R. (1976). Suppression of food intake in diabetic rats by voluntaryconsumption and intrahypothalamic injection of glucose. Physiology and Behavior, 16,763–770.

Rodin, J., Reed, D. & Jamner, L. (1988). Metabolic effects of fructose and glucose: Implicationsfor food intake. American Journal of Clinical Nutrition, 47, 683–689.

Sclafani, A. & Ackroff, K. (1994). Glucose- and fructose-conditioned flavor preferences inrats: Taste versus postingestive conditioning. Physiology and Behavior, 56, 339–405.

Sclafani, A., Cardieri, C., Tucker, K., Blusk, D. & Ackroff, K. (1993). Intragastric glucosebut not fructose conditions robust flavor preferences in rats. American Journal ofPhysiology, 265, R320–R325.

Tepper, B. J. & Friedman, M. I. (1991). Altered acceptability of and preference for sugarsolutions by diabetic rats is normalized by high-fat diet. Appetite, 16, 25–38.


Tordoff, M. G., Tepper, B. J. & Friedman, M. I. (1987). Food flavor preferences producedby drinking glucose and oil in normal and diabetic rats: Evidence for conditioning basedon fuel oxidation. Physiology and Behavior, 41, 481–487.

Tordoff, M. I., Ulrich, P. M. & Sandler, F. (1990). Flavor preferences and fructose: Evidencethat the liver detects the unconditioned stimulus for calorie-based learning. Appetite, 14,29–44.

Van den Berghe, G. (1978). Metabolic effects of fructose in the liver. In B. L. Horecker &E. R. Stadtman (Eds.), Current topics in cellular regulation. Vol. 13. Pp. 97–135. NewYork: Academic Press.

VanderWeele, D. A., Deems, R. O. & Kanarek, R. B. (1990). Insulin modifies flavor aversionsand preferences in real- and sham-feeding rats. American Journal of Physiology, 259,R823–R828.

Received 18 March 1996 accepted 2 July 1996

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Diabetic Rats Prefer Glucose-paired Flavors over Fructose-paired Flavors