Kevin P. Myers

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.

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.

Robust preference for a flavor paired with intragastric glucose acquired in a single trial

Rats learn to prefer flavors followed by postingestive action of nutrients. This experiment demonstrates that such preferences can be acquired with only a single, brief pairing of a novel flavor with intragastric (IG) glucose infusion. Male rats with IG catheters consumed unflavored saccharin in daily 10-min sessions, and then received in counterbalanced order on separate days a single pairing of coffee- or vinegar-flavored saccharin with IG glucose, and of the opposite flavor with IG water. Rats subsequently preferred the glucose-paired flavor in a choice test in the absence of glucose infusion. Preference was robust, persisting through repeated non-reinforced testing.

Reinforcing and aversive effects of caffeine measured by flavor preference conditioning in caffeine-naive and caffeine-acclimated rats.

Literature on the stimulus properties of caffeine in rats and humans has described both reinforcing and aversive effects. But some disagreement exists regarding whether caffeine is an effective positive reinforcer for caffeine-naive individuals, and how its stimulus properties change with habitual consumption. These experiments measured the reinforcing/aversive effects of caffeine for rats across a range of concentrations, assayed by conditioned aversion or preference for caffeine-paired flavors, and investigated changes in preference/aversion after extensive prior consumption. In the first two experiments, caffeine-naive rats were trained in sessions alternating daily between a distinctly flavored palatable solution (CS+) containing caffeine (0.07-0.25 mg/ml, yielding actual doses of approximately 4-31 mg/kg bodyweight) and a differently flavored palatable solution (CS-) without caffeine. In post-conditioning two-bottle choice tests between the CS+ and CS- flavors a clear preference/aversion function was apparent across the range of doses. In a third experiment, extensive acclimation to daily caffeine consumption prior to flavor-caffeine pairing significantly altered the preference/aversion function, apparently by reducing the aversiveness of higher doses, not increasing reinforcement by a low dose. These experiments provide additional evidence for an inherent reinforcing effect for naive rats, and also an effect of prior caffeine consumption history.

Investigation into the specificity of angiotensin II-induced behavioral desensitization.

Angiotensin II (AngII) plays a key role in maintaining body fluid homeostasis. The physiological and behavioral effects of central AngII include increased blood pressure and fluid intake. In vitro experiments demonstrate that repeated exposure to AngII reduces the efficacy of subsequent AngII, and behavioral studies indicate that prior icv AngII administration reduces the dipsogenic response to AngII administered later. Specifically, rats given a treatment regimen of three icv injections of a large dose of AngII, each separated by 20 min, drink less water in response to a test injection of AngII than do vehicle-treated controls given the same test injection. The present studies were designed to test three potential explanations for the reduced dipsogenic potency of AngII after repeated administration. To this end, we tested for motor impairment caused by repeated injections of AngII, for a possible role of visceral distress or illness, and for differences in the pressor response to the final test injection of AngII. We found that repeated injections of AngII neither affected drinking stimulated by carbachol nor did they produce a conditioned flavor avoidance. Furthermore, we found no evidence that differences in the pressor response to the final test injection of AngII accounted for the difference in intake. In light of these findings, we are able to reject these three explanations for the observed behavioral desensitization, and, we suggest instead that the mechanism for this phenomenon may be at the level of the receptor.

Enhanced flavor–nutrient conditioning in obese rats on a high-fat, high-carbohydrate choice diet

Through flavor-nutrient conditioning rats learn to prefer and increase their intake of flavors paired with rewarding, postingestive nutritional consequences. Since obesity is linked to altered experience of food reward and to perturbations of nutrient sensing, we investigated flavor-nutrient learning in rats made obese using a high fat/high carbohydrate (HFHC) choice model of diet-induced obesity (ad libitum lard and maltodextrin solution plus standard rodent chow). Forty rats were maintained on HFHC to induce substantial weight gain, and 20 were maintained on chow only (CON). Among HFHC rats, individual differences in propensity to weight gain were studied by comparing those with the highest proportional weight gain (obesity prone, OP) to those with the lowest (obesity resistant, OR). Sensitivity to postingestive food reward was tested in a flavor-nutrient conditioning protocol. To measure initial, within-meal stimulation of flavor acceptance by post-oral nutrient sensing, first, in sessions 1-3, baseline licking was measured while rats consumed grape- or cherry-flavored saccharin accompanied by intragastric (IG) water infusion. Then, in the next three test sessions they received the opposite flavor paired with 5 ml of IG 12% glucose. Finally, after additional sessions alternating between the two flavor-infusion contingencies, preference was measured in a two-bottle choice between the flavors without IG infusions. HFHC-OP rats showed stronger initial enhancement of intake in the first glucose infusion sessions than CON or HFHC-OR rats. OP rats also most strongly preferred the glucose-paired flavor in the two-bottle choice. These differences between OP versus OR and CON rats suggest that obesity is linked to responsiveness to postoral nutrient reward, consistent with the view that flavor-nutrient learning perpetuates overeating in obesity.

The convergence of psychology and neurobiology in flavor-nutrient learning

Flavor evaluation is influenced by learning from experience with foods. One main influence is flavor-nutrient learning (FNL), a Pavlovian process whereby a flavor acts as a conditioned stimulus (CS) that becomes associated with the postingestive effects of ingested nutrients (the US). As a result that flavor becomes preferred and intake typically increases. This learning powerfully influences food choice and meal patterning. This paper summarizes how research elucidating the physiological and neural substrates of FNL has progressed in parallel with work characterizing how FNL affects perception, motivation, and behavior. The picture that emerges from this work is of a robust system of appetition (a term coined by Sclafani in contrast to the better-understood satiation signals) whereby ingested nutrients sensed in the gut evoke positive motivational responses. Appetition signals act within a meal to promote continued intake in immediate response to gut feedback, and act in the longer term to steer preference towards sensory cues that predict nutritional consequences.