Anthony Sclafani

Dietary obesity in adult rats: Similarities to hypothalamic and human obesity syndromes

Abstract Normal adult female rats fed a variety of supermarket foods in addition to lab chow rapidly gained weight and became obese compared to rats fed only lab chow. Group housing the animals in an enriched environment did not alter the development of dietary obesity, but housing the rats in activity wheels reduced, although did not prevent, the obesity. The dietary obese rats did not normally defend their excessive weights since they were less willing to eat quinine diets, worked less for food, failed to increase their activity when deprived, and regained their weight at a slower rate following a fast than did controls. The similarity between this behavioral pattern and that displayed by hypothalamic obese rats and overweight humans is discussed.

Carbohydrate taste, appetite, and obesity: An overview

This paper reviews previous research on sugar appetite and sugar-induced overeating and obesity in the rat, and previews new findings reported in this issue on the rats taste and appetite for starch and starch-derived polysaccharides. A variety of behavioral methods demonstrate that rats are very attracted to the taste of sugars. At low molar concentrations their order of preference is maltose greater than sucrose greater than glucose = fructose, while at high concentrations it is sucrose greater than maltose greater than glucose = fructose. New findings indicate that rats are also very attracted to starch-derived polysaccharides, such as Polycose. In fact, Polycose is preferred to sucrose and maltose at low concentrations, and is second only to sucrose in preference at high concentrations. Furthermore, rats taste Polycose as qualitatively different from sucrose. These and other findings suggest that rats as well as other rodents have different taste receptors for sugar and starch. The role of these two taste systems in carbohydrate-induced overeating and obesity is discussed. Rats tend to overeat and become obese when fed sugar or polysaccharide diets, but this response depends critically on the form of the diet. Presenting the carbohydrate as a solution or gel supplement to the diet is much more effective in promoting hyperphagia and obesity than is presenting it as a powder supplement or as part of a composite diet. The differential response to hydrated and dehydrated foods may occur because carbohydrates are absorbed at a faster rate in hydrated forms than in dehydrated forms. The postingestive actions of carbohydrates also modulate the rats preference for carbohydrate tastes and flavors. Other factors that influence carbohydrate appetite and intake include the availability of the carbohydrate source and the macronutrient composition of the diet. Thus, several factors in addition to taste determine the response of rats to carbohydrate foods.

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

The discovery of taste and nutrient receptors (chemosensors) in the gut has led to intensive research on their functions. Whereas oral sugar, fat, and umami taste receptors stimulate nutrient appetite, these and other chemosensors in the gut have been linked to digestive, metabolic, and satiating effects that influence nutrient utilization and inhibit appetite. Gut chemosensors may have an additional function as well: to provide positive feedback signals that condition food preferences and stimulate appetite. The postoral stimulatory actions of nutrients are documented by flavor preference conditioning and appetite stimulation produced by gastric and intestinal infusions of carbohydrate, fat, and protein. Recent findings suggest an upper intestinal site of action, although postabsorptive nutrient actions may contribute to flavor preference learning. The gut chemosensors that generate nutrient conditioning signals remain to be identified; some have been excluded, including sweet (T1R3) and fatty acid (CD36) sensors. The gut-brain signaling pathways (neural, hormonal) are incompletely understood, although vagal afferents are implicated in glutamate conditioning but not carbohydrate or fat conditioning. Brain dopamine reward systems are involved in postoral carbohydrate and fat conditioning but less is known about the reward systems mediating protein/glutamate conditioning. Continued research on the postoral stimulatory actions of nutrients may enhance our understanding of human food preference learning.

Glucose- and fructose-conditioned flavor preferences in rats: taste versus postingestive conditioning.

Flavor preferences conditioned by glucose and fructose were compared using two training methods. With the simultaneous method preferences can be reinforced by the flavor and/or the postingestive consequences of nutrients, whereas with the delayed method preferences are reinforced only by postingestive nutritive effects. In Experiment 1, food-deprived rats displayed similar preferences for flavors (CS+) added to an 8% glucose or 8% fructose solution over flavors (CS-) added to a noncaloric saccharin solution (simultaneous conditioning). Other rats learned to prefer a CS+ flavor paired with the delayed (10 min) presentation of 8% glucose over a CS- flavor paired with delayed saccharin. Fructose failed to condition a flavor preference with the delayed paradigm. Taken together, these data suggest that the preference for a flavor mixed in a fructose solution is reinforced by the sweet taste, not the postingestive effects of the sugar. Experiment 2 tested this idea by devaluing the taste of the sugar solutions by quinine adulteration. Rats initially avoided both glucose-quinine and fructose-quinine solutions in favor of a saccharin solution. Following one-bottle training, they came to prefer the glucose-quinine but not the fructose-quinine solution over the saccharin solution. The glucose-trained rats also showed stronger preferences for sucrose-quinine solutions than did the fructose-trained rats. These findings, along with other recent data, indicate that fructose-conditioned preferences are based primarily on the sugars palatable taste. Glucose, in contrast, can condition strong preferences based on its taste as well as its postingestive actions.

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.

Conditioned flavor avoidance, preference, and indifference produced by intragastric infusions of galactose, glucose, and fructose in rats.

The postingestive reinforcing and satiating effects of intragastric (i.g.) infusions of 16% galactose, glucose, and fructose were compared in adult female rats. In Experiment 1, food-restricted rats were trained to drink (30 min/day) flavored solutions (the CS+Gal and CS+Glu) paired with intragastric (i.g.) infusions of galactose and glucose; other flavors (the CS-) were paired with IG water infusions. In subsequent choice tests, the rats strongly preferred (91%) the CS+Glu to the CS-, but avoided the CS+Gal (21%) in favor of the CS-. In Experiment 2, the rats were trained with a CS+Fru paired with i.g. fructose infusions and a CS- paired with i.g. water. In the choice test they consumed similar amounts of CS+Fru and CS- (CS+Fru preference = 51%). In other choice tests they preferred the CS+Glu (>80%) to CS+Fru and CS+Gal, and the CS+Fru (81%) to CS+Gal. Satiation tests were performed in Experiment 3 by adapting the rats to drink a 3% sugar + 0.2% saccharin solution paired with i.g. water infusions (30 min/day). On different test days 16% sugar instead of water was infused. IG galactose, glucose, and fructose produced comparable reductions in sugar+saccharin intake in the first test session. These findings demonstrate that, while the three sugars had similar satiating effects, they differed substantially in their postingestive flavor conditioning effects. The glucose and fructose results confirm prior data indicating that only glucose generates potent postingestive reinforcing stimuli. The galactose-induced flavor avoidance indicates that this sugar has a negative postingestive consequence. This may be due to the slow and incomplete hepatic metabolism of this sugar in adult rats. Conceivably, galactose intolerance may contribute to the lactose avoidance in adult animals.

Reinforcement value of sucrose measured by progressive ratio operant licking in the rat.

Progressive ratio (PR) schedules, which require increasing numbers of responses for successive reinforcements, are widely used to measure the reward value of foods, fluids, and drugs in operant lever-pressing tasks. The present study evaluated a PR operant licking task as a measure of sweet taste reward. In Experiment 1, food deprived rats were offered sucrose to drink on PR lick or fixed ratio (FR) lick schedules (30 min/day). In Experiment 2, nondeprived rats were offered sucrose to drink on PR or FR schedules and free access to water and food 23 h/day. In both experiments, the FR rats increased and then decreased their sucrose solution intake as concentration increased from 1% to 32% or 64%. The PR rats, in contrast, showed a near-linear increase in sucrose solution intake, lick rates, and break points (highest ratio completed) as a function of sucrose concentration. The PR rats drank less sucrose than did the FR rats although they emitted more total licks at the highest concentration tested. These results are similar to those reported with PR lever-pressing tasks. Thus, PR operant licking, which requires minimal training and equipment, is a useful alternate measure of fluid reward in rodents.

Post-ingestive positive controls of ingestive behavior

Post-ingestive negative controls of ingestive behavior are well characterized. Nutrients act in the gut to inhibit meal size by direct actions on feeding and by conditioning a satiation response to orosensory (flavor) stimuli. Accumulating evidence indicates that there are also post-ingestive positive controls of ingestion that operate by conditioning flavor preference and increased acceptance. In several experiments rats trained to consume a flavored solution paired with intragastric carbohydrate infusions significantly increased their solution intake. Drinking bout size and number, and lick rates and burst size were also increased by carbohydrate infusions. Whether intake is stimulated or inhibited by post-ingestive nutrient actions depends upon several factors, including most notably nutrient concentration. Post-ingestive positive controls need to be incorporated into theoretical models of ingestive behavior.

How food preferences are learned: laboratory animal models

Food selection represents a major challenge for omnivorous species. Faced with a variety of potential foodstuffs, many beneficial and some deleterious, the omnivore must decide which to eat and which to reject. The select-reject decision process involves an evaluation of the sensory characteristics of the foodstuff, particularly its flavour (i.e. taste, odour and texture). Innate predispositions such as a sweet-taste preference and bitter-taste aversion influence this process. With experience, animals refine their preferences as they associate the flavours of specific foods with the foods’ post-ingestive consequences. Social interactions also contribute to the food choices of many animal species. Until recently, most research has focused on conditioned food aversions which readily develop when animals experience gastrointestinal malaise after eating a new food (Braveman & Bronstein, 1985). It is now well documented that strong food preferences can also be learned as animals experience the positive nutritive effects of foods. As reviewed below, a variety of models have been developed using laboratory rats to reveal the intricacies of food-preference learning.

The effects of pimozide on the consumption of a palatable saccharin-glucose solution in the rat ☆

Two experiments investigated the role of dopamine in reward mechanisms by examining the effects of the specific dopamine receptor blocker pimozide on drinking behavior in the rat. In Experiment 1, the effects of pimozide on the consumption of a palatable saccharin-glucose solution were compared to the effects of quinine adulteration of the same solution. Pimozide and quinine both reduced 30 min/day consumption, decreased lick rate early in the drinking session and reduced lick efficiency in a dose related manner. In Experiment 2, the effects of pimozide on the consumption of a saccharin-glucose solution and water were compared in thirsty and nonthirsty rats. Pimozide suppressed the consumption of both water and the saccharin-glucose solution in a dose related manner. However, saccharin-glucose solution intake was suppressed more than water intake, and this effect was independent of thirst drive. The drug also decreased lick rate early in the drinking session and lick efficiency. The results are discussed in terms of the reward and sensory-motor deficits produced by dopamine receptor blocking agents.