Oromotor and somatic taste reactivity during sucrose meals reveals internal state and stimulus palatability after gastric bypass in rats.

After Roux-en-Y gastric bypass (RYGB), rats consume less high-energy foods and fluids, though whether this reflects a concomitant change in palatability remains unclear. By measuring behavior during intraorally delivered liquid meals across days (1 water, 8 sucrose sessions), we showed that RYGB rats (RYGB, n = 8/sex) consumed less 1.0 M sucrose than their sham surgery counterparts (SHAM, n = 8 males, n = 11 females) but displayed similarly high levels of ingestive taste reactivity responses at the start of infusions. Relative to water, both groups increased intake of sucrose, and ingestive responses were dominated by tongue protrusions rather than mouth movements. Thus, RYGB animals still found sucrose palatable despite consuming less than the SHAM group. As the intraoral infusion progressed but before meal termination, aversive behavior remained low and both RYGB and SHAM animals showed fewer ingestive responses, predominantly mouth movements as opposed to tongue protrusions. This shift in responsiveness unrelated to surgical manipulation suggests negative alliesthesia, or a decreased palatability, as rats approach satiation. Notably, only in RYGB rats, across sessions, there was a striking emergence of aversive behavior immediately after the sucrose meal. Thus, although lower intake in RYGB rats seems independent of the hedonic taste properties of sucrose, taste reactivity behavior in these animals immediately after termination of a liquid meal appears to be influenced by postoral events and reflects a state of nimiety or excessive consumption. Measurement of taste reactivity behaviors during an intraorally delivered meal represents a promising way to make inferences about internal state in nonverbal preclinical models.

Taste- and flavor-guided behaviors following Roux-en-Y gastric bypass in rodent models.

Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficacious treatments for obesity, but the behavioral and physiological mechanisms through which it enacts its effects are not completely understood. The weight loss that follows RYGB surgery is due to some extent to decreased caloric intake. The perception of flavor and the sense of taste undoubtedly contribute to ingestion, and changes in taste sensation and flavor perception may, even in part, propel the altered feeding seen after RYGB surgery. Measuring observable behavior in non-human animal models of RYGB surgery is an objective way by which to evaluate underlying mechanism, including the influence of flavor and taste to intake changes after RYGB surgery, as well as the interaction of flavor and taste with post-oral consequences and learning phenomena. Collectively, the data in rodent models support the conclusion that neither palatability nor motivational potency are reduced following RYGB surgery. Indeed, rats still typically show preference for sweet and fatty solids and liquids, and positive flavor-guided hedonic responses for these substances remain stable in some tests. However, preference for these foods and fluids is reduced, and flavor-guided behaviors after long-term tests are reorganized. These patterns suggest that, while rats are still motivated to consume sweet and fatty consumables and find them palatable, they learn to limit their intake of them to avoid undesirable post-oral consequences. Examination of these interactions and elucidating their physiologic correlates may maximize the efficacy of RYGB surgery and/or promote the development of alternative or supplemental treatments.

Roux-en-Y gastric bypass in rats progressively decreases the proportion of fat calories selected from a palatable cafeteria diet.

Roux-en-Y gastric bypass surgery (RYGB) decreases caloric intake in both human patients and rodent models. In long-term intake tests, rats decrease their preference for fat and/or sugar after RYGB, and patients may have similar changes in food selection. Here we evaluated the impact of RYGB on intake during a "cafeteria"-style presentation of foods to assess if rats would lower the percentage of calories taken from fat and/or sugar after RYGB in a more complex dietary context. Male Sprague-Dawley rats that underwent either RYGB or sham surgery (Sham) were presurgically and postsurgically given 8-days free access to four semisolid foods representative of different fat and sugar levels along with standard chow and water. Compared with Sham rats, RYGB rats took proportionally fewer calories from fat and more calories from carbohydrates; the latter was not attributable to an increase in sugar intake. The proportion of calories taken from protein after RYGB also increased slightly. Importantly, these postsurgical macronutrient caloric intake changes in the RYGB rats were progressive, making it unlikely that the surgery had an immediate impact on the hedonic evaluation of the foods and strongly suggesting that learning is influencing the food choices. Indeed, despite these dietary shifts, RYGB, as well as Sham, rats continued to select the majority of their calories from the high-fat/high-sugar option. Apparently after RYGB, rats can progressively regulate their intake and selection of complex foods to achieve a seemingly healthier macronutrient dietary composition.

Reduced sweet and fatty fluid intake after Roux-en-Y gastric bypass in rats is dependent on experience without change in stimulus motivational potency.

Here we assessed how intake reductions induced by Roux-en-Y gastric bypass surgery (RYGB) occur within and across access periods by examining drinking microstructure. After training, RYGB (n = 8-10) or sham-operated (SHAM, n = 12) rats were given 60-min access first to 0.3 M sucrose, then to 5% Intralipid, and finally to milk-chocolate Ensure Plus across 5 days each. Initially, total licks taken during the first meal of sucrose and Intralipid by RYGB and SHAM rats did not differ, but, across subsequent test periods, RYGB rats licked less than SHAM rats. First Ensure meal size also did not differ between RYGB and SHAM rats, but SHAM rats increased licking across test periods while the behavior of RYGB rats remained stable. The intake differences between the surgical groups, when they occurred, were most often due to smaller burst sizes in RYGB rats. Importantly, the surgical-group difference in sucrose and Intralipid intakes could not be explained by altered palatability of these solutions because, throughout testing, both groups had similar early meal licking behavior thought to represent the motivational potency of stimulus orosensory features. Although, overall, RYGB rats displayed lower early meal licking of Ensure relative to the SHAM rats, this appeared to be driven primarily by increases in the latter group across test periods; the RYGB group stayed relatively stable. Collectively, these results suggest that some level of postoral experience with these stimuli and/or their components is necessary before intake differences emerge between surgical groups, and, even when differences occur, often immediate taste-motivated ingestive behavior remains unaltered.

Gastric bypass in rats does not decrease appetitive behavior towards sweet or fatty fluids despite blunting preferential intake of sugar and fat.

After Roux-en-Y gastric bypass (RYGB) surgery, patients report consuming fewer fatty and dessert-like foods, and rats display blunted sugar and fat preferences. Here we used a progressive ratio (PR) task in our rat model to explicitly test whether RYGB decreases the willingness of rats to work for very small amounts of preferred sugar- and/or fat-containing fluids. In each of two studies, two groups of rats - one maintained on a high-fat diet (HFD) and standard chow (CHOW) and one given CHOW alone - were trained while water-deprived to work for water or either Ensure or 1.0M sucrose on increasingly difficult operant schedules. When tested before surgery while nondeprived, HFD rats had lower PR breakpoints (number of operant responses in the last reinforced ratio) for sucrose, but not for Ensure, than CHOW rats. After surgery, at no time did rats given RYGB show lower breakpoints than SHAM rats for Ensure, sucrose, or when 5% Intralipid served postoperatively as the reinforcer. Nevertheless, RYGB rats showed blunted preferences for these caloric fluids versus water in 2-bottle preference tests. Importantly, although the Intralipid and sucrose preferences of RYGB rats decreased further over time, subsequent breakpoints for them were not significantly impacted. Collectively, these data suggest that the observed lower preferences for normally palatable fluids after RYGB in rats may reflect a learned adjustment to altered postingestive feedback rather than a dampening of the reinforcing taste characteristics of such stimuli as measured by the PR task in which postingestive stimulation is negligible.

Systemic modulation of serotonergic synapses via reuptake blockade or 5HT1A receptor antagonism does not alter perithreshold taste sensitivity in rats.

Systemic blockade of serotonin (5HT) reuptake with paroxetine has been shown to increase sensitivity to sucrose and quinine in humans. Here, using a 2-response operant taste detection task, we measured the effect of paroxetine and the 5HT1A receptor antagonist WAY100635 on the ability of rats to discriminate sucrose, NaCl, and citric acid from water. After establishing individual psychometric functions, 5 concentrations of each taste stimulus were chosen to represent the dynamic portion of the concentration-response curve, and the performance of the rats to these stimuli was assessed after vehicle, paroxetine (7mg/kg intraperitoneally), and WAY100635 (0.3mg/kg subcutaneously; 1mg/kg intravenously) administration. Although, at times, overall performance across concentrations dropped, at most, 5% from vehicle to drug conditions, no differences relative to vehicle were seen on the parameters of the psychometric function (asymptote, slope, or EC50) after drug administration. In contrast to findings in humans, our results suggest that modulation of 5HT activity has little impact on sucrose detectability at perithreshold concentrations in rats, at least at the doses used in this task. In the rat model, the purported paracrine/neurocrine action of serotonin in the taste bud may work in a manner that does not impact overt taste detection behavior.

The selective serotonin reuptake inhibitor paroxetine decreases breakpoint of rats engaging in a progressive ratio licking task for sucrose and quinine solutions.

Increased serotonergic activity has been shown to reduce motivation to ingest, which may involve, in part, gustatory processes. Here, we examined the effect of paroxetine, a selective serotonin reuptake inhibitor, on appetitive responding for a preferred and an avoided taste solution using a progressive ratio (PR) task in which licking was employed as the operant. Male Sprague-Dawley rats (n = 8/taste stimulus) were trained to respond for a concentration series of sucrose or quinine on fixed and PR schedules of reinforcement. Performance for sucrose was assessed while the rats were partially food- and water-restricted and nondeprived, and performance for water and quinine was assessed while the rats were water-deprived. Then, the rats were injected with vehicle (10% dimethyl sulfoxide, 1mL/kg intraperitoneal [ip], -1h) or paroxetine (5mg/kg), and their responding on a PR schedule for sucrose measured when the rats were nondeprived or for water and quinine when the rats were water-deprived. Paroxetine decreased breakpoint, which was defined as the number of operant (e.g., dry) licks in the final reinforced ratio, for water, quinine, and sucrose. This demonstrates that a general systemic increase in serotonergic activity decreases the appetitive-based responses to both preferred and nonpreferred fluids under different deprivation states.

Food selection and taste changes in humans after Roux-en-Y gastric bypass surgery: a direct-measures approach.

It has been suggested that the weight loss seen in individuals who receive Roux-en-Y gastric bypass surgery may be due, at least in part, to changes in patient food selection, and that this change may stem from effects of the operation on the sense of taste. In this review, we evaluate the literature examining postoperative changes in food intake and food choice. While some evidence suggests that gastric bypass leads to altered food selection and taste perceptions, a clear picture regarding these changes remains to be elucidated and is blurred by inconsistencies, which may be rooted in the diverse subject pools within and between studies as well as in the indirect measures used to assess ingestive behavior. We argue that complementing current assessment tools with more direct measures of intake, food selection, and taste-related behavior might help provide some clarity and also facilitate translation between findings from animal models, in which similar measures are available, and clinical research.

The selective serotonin reuptake inhibitor paroxetine does not alter consummatory concentration-dependent licking of prototypical taste stimuli by rats.

Serotonin and the 5HT(1A) receptor are expressed in a subset of taste receptor cells, and the 5HT(3) receptor is expressed on afferent fibers innervating taste buds. Exogenous administration of the selective serotonin reuptake inhibitor, paroxetine, has been shown to increase taste sensitivity to stimuli described by humans as sweet and bitter. Serotonergic agonists also decrease food and fluid intake, and it is possible that modulations of serotonin may alter taste-based hedonic responsiveness; alternatively, or in combination, serotonin may interact with physiological state to impact ingestive behavior. In this study, the unconditioned licking of prototypical taste stimuli by rats in brief-access taste tests was assessed following paroxetine administration (0.3-10 mg/kg intraperitoneal). We also measured sucrose licking by rats in different deprivation states after paroxetine (5 mg/kg). In neither experiment did we find any evidence of an effect of paroxetine on licking relative to water to any of the taste stimuli in the brief-access test at doses that decreased food intake. However, in some conditions, paroxetine decreased trials initiated to tastants. Therefore, a systemic increase in serotonin via paroxetine administration can decrease appetitive behavior in brief-access tests but is insufficient to alter taste-guided consummatory behavior.

Citric acid and quinine share perceived chemosensory features making oral discrimination difficult in C57BL/6J mice.

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical.

Selection of a palatable dietary option is not preferentially reduced by cannabinoid CB1 receptor antagonist AM251 in female C57Bl/6J mice.

We previously showed in female rats that administration of the cannabinoid CB1 receptor antagonist AM251 reduced energy intake by selectively decreasing consumption of a palatable dietary option in comparison to a standard maintenance chow. In the present study we sought to generalize these findings to mice. We presented 6 week old female C57Bl/6J mice with daily 8 h access to a sugar fat whip dietary option along with ad libitum access to moist chow. Mice were injected daily with either vehicle (equal parts polyethylene glycol and saline, 2 ml/kg) or one of three doses of AM251 (1, 3, or 10 mg/kg). Food intake and body weight were measured daily for 21 days. Although 8 h access to sugar fat whip did not induce overconsumption in female mice, AM251 reduced their energy intake and body weight in a dose-dependent manner. The decrease in energy intake occurred for both chow and sugar fat whip. This difference from results in rats suggests that the effect of AM251 on palatable food intake may only be evident in models that induce overconsumption and/or that rats and mice may react differently to CB1 receptor antagonists.

Cannabinoid-1 receptor antagonists reduce caloric intake by decreasing palatable diet selection in a novel dessert protocol in female rats.

Although many feeding protocols induce obesity, few use multiple foods to analyze diet selection within a single group of animals. To this end, we describe a protocol using time-limited access to a dessert that induces hyperphagia and body weight gain while allowing simple analysis of diet selection. Female retired breeder Sprague-Dawley rats were provided with ad libitum access to standard moist chow (1.67 kcal/g) and daily 8-h nocturnal access to either a sugar gel (SG; 0.31 kcal/g) or sugar fat whip (SFW; 7.35 kcal/g) for 15 days, and food intake and body weight were measured daily. Rats given SFW reduced moist chow intake but not enough to compensate for the large amount of calories consumed from SFW, and thus gained weight. We use this SFW overconsumption protocol to investigate the hypothesis that cannabinoid (CB)1 receptor antagonists reduce caloric intake by selectively decreasing consumption of palatable foods. In two experiments, female retired breeder Sprague-Dawley rats were injected with either Rimonabant (1 mg/kg ip) or vehicle (equal parts polyethylene glycol and saline, 1 ml/kg ip) for 7 days, or one of three doses of AM251 (0.3, 1.0, or 3.0 mg/kg ip), or vehicle for 15 days; food intake and body weight were measured daily. Both Rimonabant and AM251 decreased 24-h caloric intake, but the reduction was specific to a decrease in SFW consumption. This supports the hypothesis that these CB1 receptor antagonists impact feeding by modulating the perception of palatability.

Feeding behavior, obesity, and neuroeconomics.

For the past 50 years, the most prevalent theoretical models for regulation of food intake have been based in the physiological concept of energy homeostasis. However, several authors have noted that the simplest form of homeostasis, stability, does not accurately reflect the actual state of affairs and most notably the recent upward trend in body mass index observed in the majority of affluent nations. The present review argues that processes of natural selection have more likely made us first and foremost behavioral opportunists that are adapted to uncertain environments, and that physiological homeostasis is subservient to that reality. Examples are presented from a variety of laboratory studies indicating that food intake is a function of the effort and/or time required to procure that food, and that economic decision-making is central to understanding how much and when organisms eat. The discipline of behavioral economics has developed concepts that are useful for this enterprise, and some of these are presented. Lastly, we present demonstrations in which genetic or physiologic investigations using environmental complexity will lead to more realistic ideas about how to understand and treat idiopathic human obesity. The fact is that humans are eating more and gaining weight in favorable food environments in exactly the way predicted from some of these models, and this has implications for the appropriate way to treat obesity.