Subdiaphragmatic vagal deafferentation fails to block the anorectic effect of hydroxycitrate

We investigated the neural mediation of the feeding suppression through orally administered hydroxycitrate (HCA) in male rats that were fed a high-glucose diet (about 48% glucose). Ten-day ad libitum food intake and body weight regain after previous body weight loss (13% of initial body weight) due to restrictive feeding were measured in rats with sham deafferentation (SHAM; n = 6), subdiaphragmatic vagal deafferentation (SDA; n = 7), and SDA plus celiac-superior mesenteric ganglionectomy (SDA/CGX; n = 9). HCA suppressed the 10-day cumulative food intake in all surgical groups and body weight regain in SDA and SDA/CGX groups. Independent of HCA, SDA and SDA/CGX rats consumed less food and gained less weight compared to SHAM rats. These results demonstrate that all vagal afferents from below the diaphragm and vagal efferents of the dorsal trunk as well as splanchnic nerves (afferents and efferents) are not necessary for the feeding-suppressive effect of HCA in this animal model. Vagal afferents, however, appear to play a role in the control of intake when a high-glucose diet is consumed after a period of restrictive feeding.     

Conditioned flavor preference and aversion: role of the lateral hypothalamus

Food-restricted rats with ibotenic acid lesions of the lateral hypothalamus (LH) and sham controls were trained to associate flavored solutions with positive or negative postingestive consequences. The LH rats learned to prefer a flavor that was paired with concurrent intragastric infusions of maltodextrin. Unlike controls, the LH rats failed to learn a preference for a flavor paired with delayed maltodextrin infusions and showed an attenuated preference for a flavor paired with concurrent fat infusions. The LH rats did not differ from controls in learning to avoid flavors paired with concurrent or delayed infusions of lithium chloride. These data indicate that the LH is not essential for all types of flavor-postingestive consequence conditioning but is critical for learning to associate flavors with delayed nutrient feedback.     

Area postrema lesions impair flavor-toxin aversion learning but not flavor-nutrient preference learning

Rats with lesions of the area postrema (APX) or sham lesions were trained to associate flavored solutions with positive or negative postingestive consequences. The APX rats were similar to controls in learning preferences for flavors paired with concurrent intragastric infusions of maltodextrin or corn oil and for a flavor paired with delayed maltodextrin infusions. In contrast, the APX rats displayed impaired aversion learning for flavors paired with toxic drug treatments (lithium chloride infusion or methylscopolamine injection). The aversion learning deficit ranged from mild to total, depending on training procedures. These findings confirm the important role of the area postrema in flavor-toxin learning but provide no evidence for its involvement in flavor-nutrient conditioning.     

Flavor preferences conditioned by intragastric nutrient infusions in food restricted and free-feeding rats

The role of deprivation state in flavor preference conditioning by nutrients was investigated in rats fitted with intragastric (IG) catheters. In different experiments, food restricted (FR) and food ad libitum (AL) groups were trained to drink one flavored solution (CS+) paired with IG infusions of maltodextrin, corn oil, or casein and another flavored solution (CS-) paired with IG water infusions. Training intakes of the CS solutions were limited to equate the exposure of the FR and AL groups. The IG nutrient infusions conditioned flavor preferences in FR and AL groups which, in three of four experiments, were of similar magnitude. Food restriction did, however, increase the overall intake of the CS+ solutions during testing. Rats trained with one CS+ while food restricted and a second CS+ while food unrestricted showed similar preferences for the two CS+ flavors. Prefeeding AL rats to satiety with chow prior to daily training sessions did not prevent them from developing a preference for a CS+ paired with IG maltodextrin. These findings indicate that the postoral actions of nutrients are reinforcing in food sated as well as hungry rats.     

Differential reinforcing and satiating effects of intragastric fat and carbohydrate infusions in rats.

Food intake and preferences are modulated by the postingestive satiating and reinforcing actions of nutrients. This experiment compared the feeding effects of isocaloric intragastric (i.g.) carbohydrate (maltodextrin) and fat (corn oil) infusions in food-restricted rats fed low-fat (12% fat kcal) or high-fat (48% fat kcal) diets. In Experiment 1, the rats were given one flavored saccharin solution (CS+C) paired with i.g. carbohydrate infusions, a second flavor (CS+F) paired with i.g. fat infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests, the rats preferred both CS+s to the CS- (68-83%) and the CS+C to the CS+F (68-70%). In Experiment 2, the feeding inhibitory effects of the nutrient infusions on an ongoing meal (satiation test) or a subsequent meal (satiety test) were compared. The intake of a palatable Polycose+saccharin solution was suppressed by a concurrent carbohydrate infusion but not by a fat infusion. Also, i.g. carbohydrate preloads suppressed the intake of a subsequent (30-180 min) mixed carbohydrate+fat test meal more than did i.g. fat preloads. The satiety effects of the fat preloads were more pronounced in rats fed the low-fat diet than in rats fed the high-fat maintenance diet. Diet composition did not reliably influence the preference conditioning and satiation effects of the nutrient infusions. These results confirm prior reports that fat is less satiating than carbohydrate, and further demonstrate that i.g. carbohydrate infusions condition a stronger flavor preference than fat infusions.     

Flavor preference conditioning as a function of fat source

Rats learn to prefer foods based, in part, on postingestive nutrient actions. This study compared the effectiveness of intragastric (IG) infusions of fat emulsions which varied in their fatty acid composition (chain length and saturation) to condition preferences for flavored saccharin solutions. In Experiment 1, food-restricted rats were trained (30 min/day) with one flavor (CS+CO) paired with IG corn oil (CO) and a second flavor (CS+MCT) paired with IG medium chain triglyceride (MCT); the fats were prepared as isocaloric emulsions. A third flavor (CS-) was paired with IG water. The rats subsequently showed a strong preference for the CS+CO (84%) and a weaker preference for the CS+MCT (65%) relative to the CS-. In a direct choice test, the CS+CO was preferred to the CS+MCT by 75%. In Experiment 2, new rats trained with flavors paired with IG corn oil and beef tallow (BT) infusions learned to prefer both the CS+CO (89%) and the CS+BT (82%) relative to the CS-, and preferred the CS+CO to the CS+BT by 67%. The same rats were trained with three new flavors paired with IG infusions of corn oil, vegetable shortening (VS), and water. The rats strongly preferred both the CS+CO (91%) and CS+VS (86%) over the CS-, and they preferred the CS+CO to the CS+VS by 64%. In Experiment 3, new rats trained with corn oil and safflower oil (SO) paired flavors preferred both the CS+CO and CS+SO to the CS-, and equally preferred the CS+CO and CS+SO in two-bottle tests. The rats were also given one-and two-bottle tests with the various fat emulsions and their preference profile was consistent with their conditioned preferences for the flavored saccharin solutions. These findings demonstrate that many different fat sources can condition flavor preferences. Fats with high polyunsaturated content and/or lower saturated fat content are the most reinforcing.     

Flavor preferences conditioned by intragastric fat infusions in rats

The present series of experiments determined if rats would learn to prefer cue flavors that were paired with intragastric (IG) infusions of fat. Adult female rats were fitted with gastric catheters and were trained to drink a flavored (CS+) solution, e.g., cherry-water, associated with IG infusions of a corn oil emulsion. On other days, an alternately flavored (CS-) solution, e.g., grape-water, was paired with IG infusions of water. The preference between the CS solutions was then assessed with 2-bottle choice tests. In Experiment 1, food-restricted rats were given saccharin-sweetened CS solutions for 10 min/day followed by IG infusions of a 7.1% oil emulsion or water. In subsequent choice tests they displayed a small (60%) but significant preference for the CS+ solution. In Experiments 2-5, rats had access to the CS solutions for 20 or 23 hr/day; drinking the CS solutions automatically triggered IG infusions of oil or water (electronic esophagus preparation). Infusions of 7.1% oil failed to produce a significant preference for the CS+ solution in rats given ad lib access to chow, and offered unsweetened CS flavors. Increasing the oil concentration (14.5% and 29%) did not facilitate the formation of a preference, nor did infusing the rats with a preingested oil emulsion. However, rats restricted to 2 hr/day access to chow, and 20 hr/day access to the CS solutions acquired a significant (85%) preference for the CS+ flavor; subsequent training and testing with saccharin-sweetened CS solutions increased the preference for the CS+ flavor to 95%. Ad lib fed rats trained with saccharin-sweetened CS solutions also developed a reliable preference (76%) for the CS+ flavor paired with IG oil; this preference persisted during four extinction tests when both CS+ and CS- flavors were paired with IG water. These results demonstrate that, as with other macronutrients (carbohydrate, protein), the postingestive effects of fats can condition flavor preferences, and suggest that the postingestive actions of nutrients play an important role in food selection and reward.     

Flavor preferences conditioned by postingestive effects of nutrients in preweanling rats

The purpose of these experiments was to determine if preweanling rats, like adults, are capable of learning to associate an arbitrary flavor with the postingestive effects of nutrients, and then demonstrate a preference for that flavor after weaning. In Experiment 1, preweanlings were trained daily from postnatal day (P) 16 through P19 with intraoral (IO) infusions of a grape or cherry flavor (CS+) mixed with 20% glucose (US), and the opposite flavor (CS-) mixed with 0.05% saccharin. After weaning, rats were given a 4-h two-bottle choice between the CS+ and CS- flavors both presented in 0.05% saccharin. Rats preferred the flavor previously paired with glucose. In Experiment 2 using similar methods, rats learned to prefer a flavor (CS+G) paired with a glucose US over a flavor (CS+S) paired with a sweeter but less nutritive sucrose US, indicating involvement of postingestive reinforcement. In Experiment 3 preweanling rats with IO and intragastric (IG) catheters were trained with a CS+ flavor paired with IG nutrient infusion, and a CS- flavor paired with no IG infusion. These rats showed no flavor preference 3 days after weaning, but did significantly prefer the CS+ flavor over the CS- flavor 10 days after weaning. Together these experiments demonstrate that neural mechanisms for flavor-nutrient associations are developed before weaning, allowing young rats to learn associations between arbitrary flavors and nutritive consequences. Thus nutrient conditioning may be one way that early experience (such as flavors from the maternal diet transmitted in milk) influences later dietary preferences.     

Flavor preferences conditioned by post-oral infusion of monosodium glutamate in rats

Monosodium glutamate (MSG), the prototypical umami source, can enhance preference for associated flavors in humans and rodents. Although MSG flavor preference has been attributed to its taste, vagally-mediated post-oral detection has also been demonstrated. Recent studies showed that water-restricted rats acquired a preference for a flavor paired with intragastric (IG) infusion of 60 mM MSG in rats. The present study extends this work by comparing MSG-based flavor conditioning in water- and food-restricted rats and testing the persistence of flavor preferences. Rats with IG catheters drank flavored solutions paired with volume-matched infusions of 60 mM MSG or water in daily 30-min sessions. Two training/test cycles were conducted, each with eight one-bottle training sessions followed by two two-bottle preference tests without infusions. Food- and water-restricted groups displayed similar preferences for the MSG-paired flavor. When non-reinforced testing was continued after the second cycle, the food-restricted group sustained its preference across three 2-day tests, but water-restricted rats lost their preference. Other food-restricted rats learned to prefer a flavor paired with intraduodenal infusion, indicating that gastric stimulation by MSG is not required. A third experiment showed that adding 2 mM of the nucleotide inosine monophosphate to the IG infusion of MSG did not significantly enhance flavor conditioning. Because MSG-based flavor preferences can be obtained with infusions that bypass the stomach, the site for detecting MSG reinforcement may be intestinal.     

Hungry, but not thirsty, rats prefer flavors paired with ethanol

The present experiments examined the reinforcing effects of an ethanol (EtOH) unconditioned stimulus (UCS) on conditioned flavor preferences in food-deprived rats and in water-deprived rats. In Experiment 1A food and water deprived animals received distinct conditioning treatments. One half of the animals were intragastrically intubated with EtOH (0.5 g/kg), and thereafter allowed 20 min free access to similar flavored drinking solutions. Remaining animals were intubated with distilled water. All animals received 15 presentations of an EtOH-paired flavor. A two-bottle preference test was subsequently used to evaluate preferences or aversions to flavors paired with EtOH in food-deprived and water-deprived animals. Results of Experiment 1A showed that food-deprived animals preferred the flavor associated with EtOH. Conversely, preferences for EtOH-paired flavors were not established in water-deprived animals. In Experiment 1B deprivational states of animals used in Experiment 1A were reversed without further drug training. Following a two week habituation period to deprivation state animals again received a two-bottle preference test to re-evaluate preferences or aversions to the EtOH-paired flavors. Results of those manipulations indicated that an ethanol aversion was established in the water-deprived animals. Those results indicated that water-deprived animals of Experiment 1B reversed their EtOH-paired flavor preference when the caloric need associated with food deprivation conditions was eliminated. Since deprivational state determined the development of EtOH preferences, the present results indicate that caloric need may play an initial role in establishing conditioned preferences for EtOH.     

Flavor preferences conditioned in C57BL/6 mice by intragastric carbohydrate self-infusion

This study determined the feasibility of conditioning flavor preferences in mice by self-administered intragastric (IG) nutrient infusions. Male C57BL/6J mice were surgically fitted with an IG catheter that was attached by a tether system to an infusion pump. The mice were given ad-libitum access to chow and a flavored solution 23 h/day. Drinking was monitored with a computerized lickometer system that controlled the infusion pumps. In Experiment 1, drinking one flavored solution (CS+, e.g., grape-saccharin) was paired with matched infusions of 8% maltodextrin, whereas drinking another solution (CS-, e.g., cherry-saccharin) was matched with water infusions across 6 one-bottle training days. During training, the mice drank more CS+ than CS-; this was due to an increase in bout size but not bout frequency. In subsequent two-bottle choice tests, the mice strongly preferred (91%) the CS+ to the CS-. Experiment 2 obtained a significant but less robust (71%) CS+ preference in mice trained with unsweetened CS solutions. These data indicate that mice, like rats, acquire an increased acceptance and preference for flavors paired with the postingestive actions of nutrients. Our understanding of flavor-nutrient learning can be advanced by studying this process in selected mouse strains and genetically modified animals.     

Conditioned acceptance and preference but not altered taste reactivity responses to bitter and sour flavors paired with intragastric glucose infusion

Nutrient-conditioned flavors preferences are thought to involve an increase in flavor palatability (hedonic evaluation). Consistent with this view is the recent finding that a sweet flavor paired with intragastric glucose infusions elicited more hedonic taste reactivity (TR) responses than did an alternative sweet flavor paired with intragastric water. The generality of this finding was examined by conditioning preferences for inherently avoided nonsweet flavors. Rats were trained in 20 h/day and then 30 min/day sessions with a CS+ flavor (sour citric acid or bitter sucrose octaacetate) paired with intragastric 16% glucose infusion, and the opposite flavor (CS-) paired with intragastric water. Glucose conditioning increased the CS+ acceptance in one-bottle tests and produced a 95% CS+ preference in two-bottle sessions. Yet, TR responses to brief intraoral infusions of the two CS flavors did not differ, even after extensive testing. Subsequent choice tests revealed that a 1% fructose solution was preferred to the CS-, whereas the CS+ was preferred to 1% and 2% fructose and equally preferred to 4%, 8%, and 16% fructose. These results indicate that strong nutrient-conditioned flavor preferences are not always associated with increased flavor palatability as measured by TR tests. Therefore, nonhedonic processes, perhaps increased incentive salience, appear to mediate the enhanced preference and acceptance conditioned by postingestive nutrient actions.     

The CS-US delay gradient in flavor preference conditioning with intragastric carbohydrate infusions

Rats are able to associate a flavor with the delayed presentation of food, but the obtained flavor preferences are often weak. The present studies evaluated the effect of delay between a flavor CS and a post-oral nutrient US on the expression of conditioned flavor preferences. In Experiment 1, rats were trained with two CS flavors: one was followed after a delay by intragastric infusion of 8% glucose, and the other was followed after the same delay by intragastric water. Rats trained with 2.5, 10, and 30-min delays expressed significant (84-68%) preferences for the glucose-paired flavor whereas rats trained with 60-min delays were indifferent (51%). Experiment 2 examined flavor conditioning over a 60-min delay using 8 or 16% Polycose based on findings that orally consumed Polycose conditions preferences at this delay interval. The 8 and 16% Polycose infusions produced significant preferences which peaked at 62% and 73%, respectively. The ability to bridge these delays may allow animals to learn about slowly digested foods.     

Flavor preferences conditioned by intragastric glucose but not fructose or galactose in C57BL/6J mice

The present study determined if mice, like rats, differ in their flavor conditioning responses to intragastric (IG) infusions of three common monosaccharide sugars. In Experiment 1, C57BL/6J mice were trained to drink a flavored saccharin solution (the CS+) paired with intragastric (IG) self-infusions of 16% glucose, fructose or galactose and a different flavored solution (the CS-) paired with IG water infusions during 22 h/day training sessions. The glucose infusions increased CS+ intakes during training and produced a strong CS+ preference (~87%) in two-bottle choice tests. In contrast, the fructose and galactose infusions reduced CS training intakes and did not condition a CS+ preference. Experiment 2 determined if reducing fructose and galactose concentration would enhance conditioning. However, IG infusions of 8% sugar also failed to condition CS+ preferences. The robust conditioning response to IG glucose confirms results obtained with rats, but the indifference of mice to IG fructose and galactose contrasts with preference and avoidance responses observed in rats. The effectiveness of glucose to condition preferences suggests an important role for glucose-specific sensors rather than gut "sweet" taste receptors in the postoral modulation of carbohydrate appetite.     

Vagal afferents mediate the feeding response to mercaptoacetate but not to the beta (3) adrenergic receptor agonist CL 316,243

To evaluate the role of subdiaphragmatic vagal afferents in the anorectic response to peripheral administration of the highly selective beta(3)-adrenergic receptor agonist CL 316,243 (CL), we tested the ability of intraperitoneal (IP) injections of CL to inhibit feeding in rats with subdiaphragmatic vagal deafferentation (SDA, n=13) or sham surgeries (SHAM, n=13). Doses of 10, 100 and 1000 ng/kg CL significantly reduced feeding by statistically similar amounts in SHAM and SDA rats. One hour after IP injection, each dose of CL also significantly increased plasma concentrations of free fatty acids and beta-hydroxybutyrate, an indicator of hepatic fatty acid oxidation (FAO), whereas 6h after injection only the two highest CL doses increased plasma beta-hydroxybutyrate. In contrast, peripheral administration of the FAO inhibitor mercaptoacetate (MA, 45.6 mg/kg IP) stimulated feeding in SHAM but not in SDA rats, extending previous data suggesting a necessary role of vagal afferents in the feeding-stimulatory effect of FAO inhibition. We conclude that subdiaphragmatic vagal afferents are essential for the feeding-stimulatory action of MA but not for the anorectic action of peripheral CL and that CL-induced increase in hepatic FAO is not essential for its feeding-inhibitory effect.     

Flavor preferences conditioned by high-fat versus high-carbohydrate diets vary as a function of session length.

Intragastric (i.g.) infusions of fat and carbohydrate condition flavor preferences in rats, but different results have been obtained in studies using pure and mixed nutrient infusions. This experiment compared the preference conditioning effects of mixed high-carbohydrate (HC) and high-fat (HF) diet infusions during short-term and long-term sessions. In Experiment 1 food-deprived rats were given one flavored saccharin solution (CS+HC) paired with i.g. infusions of an HC liquid diet, a second flavor (CS+HF) paired with HF diet infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests (30 min/day), the rats preferred both CS+s to the CS- and preferred the CS+HC to the CS+HF. In Experiment 2, the same rats were trained and tested with the CSs and paired infusions during 22 h/day sessions with chow available ad lib. Both CS+s were again preferred to the CS-, but now the CS+HF was preferred to the CS+HC. When given additional 30-min choice sessions in Experiment 3 the rats showed no reliable preference for the CS+HC versus CS+HF under food-deprived or ad lib conditions. In Experiment 4, the rats were given 22-h CS+HC versus CS+HF choice sessions every other day. They showed no reliable CS preference during the first 30 min of each session, but reliably preferred the CS+HF during the remaining 21.5 h. These findings indicate that previously reported differences in preferences conditioned by pure versus mixed nutrient infusions are due to training procedures (session length, deprivation state) rather than to the type of nutrient infusions per se. The rats displayed different CS+HF versus CS+HC preferences as a function of test duration even after being given both short- and long-term training. Thus, short-term choice tests do not always predict the long-term intakes and preferences for high-fat and high-carbohydrate foods.     

Flavor preferences conditioned by intragastric polycose infusions: a detailed analysis using an electronic esophagus preparation

The present series of experiments examined the rat's conditioned preference for flavors associated with intragastric (IG) Polycose infusions. Adult female rats were fitted with two chronic intragastric catheters and were trained to drink flavored water (CS+; e.g., cherry-water) paired with IG infusions of 32% Polycose. On alternate days a different flavor (CS-; grape-water) was paired with IG water infusions. The flavored water and chow were available 23 hr/day. In subsequent two-choice tests the rats displayed strong preferences for the CS+ flavor (up to 98%). The CS+ preference persisted for several weeks during extinction tests when both the CS+ and CS- were paired with IG water or with no infusions. The rats also preferred the CS+ to plain water which contrasts with the mild aversion naive rats display to the flavored water. The acquired preference for the CS+ flavor was not as strong, however, as the rats' innate preferences for the taste of saccharin or Polycose. Also, unlike their response to saccharin and Polycose, the rats' acceptance (absolute intake) of the CS+ flavor was not elevated. CS+ intake was increased, though, when saccharin was added to the flavored water. The rats reversed their flavor preference when the reinforcement contingencies were reversed. Also, in the absence of unique flavor cues, the rats learned to prefer, apparently based on somatosensory cues, the sipper tube that was paired with IG Polycose infusions. The effects of flavor and IG Polycose infusions on drinking patterns and caloric intake are also described.     

Dopamine and learned food preferences

An early study performed in Bart Hoebel's laboratory suggested that dopamine (DA) signaling in the nucleus accumbens was involved in learned flavor preferences produced by post-oral nutritive feedback. This paper summarizes our studies investigating the role of DA in flavor preference conditioning using selective DA receptor antagonists. Food-restricted rats were trained to prefer a flavored saccharin solution (CS+) paired with intragastric (IG) sugar infusions over a flavored saccharin solution (CS−) paired with water infusions. Systemic injections of a D1-like receptor antagonist (SCH23390), but not a D2-like receptor antagonist (raclopride) during training blocked flavor preference learning. Neither drug prevented the expression of an already learned preference except at high doses that greatly suppressed total intakes. Central sites of action were examined by local microinjections of SCH23390 (12 nmol) during flavor training or testing. Drug infusions in the nucleus accumbens, amygdala, medial prefrontal cortex, or lateral hypothalamus during training blocked or attenuated CS+ flavor conditioning by IG glucose infusions. The same drug dose did not suppress the expression of a learned CS+ preference. The findings suggest that DA signaling within different components of a distributed brain network is involved in sugar-based flavor preferences. A possible role of DA in conditioned increases in flavor acceptance is discussed.     

Some failures of intragastric NaCl infusions to support flavor preference learning

Rats can acquire conditioned flavor preferences based on the postingestive delivery of energy-rich nutrients. Here, we tried to condition flavor preferences to the postingestive delivery of the nutrient, sodium. Three experiments were conducted. In one, sodium-depleted rats were allowed to choose between two arbitrary flavors for 8 days. Ingestion of one of the flavors initiated infusions of one of two volumes of 150 mM NaCl, whereas ingestion of the other flavor had no effect. The rats showed no preference for the flavor paired with NaCl infusion. In another, sodium-depleted rats were given two pairs of 24-h one-bottle training trials. Ingestion of the flavor presented during one trial initiated infusions of water or one of four concentrations of NaCl (75, 150, 300 or 450 mM NaCl). Ingestion of the flavor presented on the other trial in each pair had no effect. In a subsequent two-bottle choice between the two flavors, the rats were either indifferent to (water, 75 and 150 mM) or avoided (300 or 450 mM) the infusion-paired flavor. In the third study, replete rats were trained as in the previous experiment with 150 mM NaCl as the infusate and tested after sodium deficiency was induced by furosemide. These animals avoided the flavor paired with NaCl infusion. We conclude that rats cannot associate an arbitrary taste with the beneficial effects of postingestive delivery of NaCl, or if they can, this occurs only under rare circumstances.     

Nutrient-conditioned flavor preference and incentive value measured by progressive ratio licking in rats

Rats develop strong preferences for flavors associated with the postingestive actions of glucose and other nutrients. This preference may involve changes in both the hedonic appeal and incentive salience of the nutrient-paired flavor. The present study used a progressive ratio (PR) operant licking task to evaluate the degree to which nutrient conditioning changes the incentive value of flavors. Food restricted rats were trained to associate one flavored saccharin solution (CS+) with intragastric glucose infusions and another flavored solution (CS-) with water infusions. The rats subsequently showed a strong preference for the CS+ in two-bottle tests and also licked more for the CS+ than CS- in PR tests. PR licking for the CS+ was similar to that for an 8% fructose solution. Together with earlier data indicating that the CS- is isopreferred to a 3% fructose solution, these findings indicate that IG glucose conditioning enhances the hedonic and incentive value of the CS+ solution so that the animal responds as if the solution had a sweeter taste.