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Biomedical subjects

Anthony Sclafani

Publications and source records attributed to Anthony Sclafani.

36 records · Page 2Linked to original sources

Oral and postoral determinants of food reward.

Tasty high-fat and high-sugar foods induce overeating and obesity in animals. To separate the roles of oral and postoral factors in food preference and consumption, recent studies have used an "electronic esophagus" preparation. With this system, when an animal drinks a flavored solution, it controls the infusion of nutrients directly into its stomach through an implanted catheter. Improving the palatability of the flavored solution increases solution intake, infused nutrient intake, and weight gain. Changing the composition of the infused nutrient (e.g., fat-carbohydrate ratio) can also alter energy intake when flavor cues are held constant. In addition, animals learn to associate flavor cues with the postoral effects of nutrients, which can significantly increase flavor preference and acceptance. In some but not all cases, conditioned preferences are associated with increased hedonic evaluation of the nutrient-paired flavor. Flavor preference conditioning by nutrients can occur in chow-sated animals and is not dependent upon an energy-depleted state. Thus, food reward is determined by oral and postoral stimuli and may override the homeostatic regulation of energy balance.

Diet↗

The relationship between food reward and satiation revisited.

The postingestive satiating action of food is often viewed as producing a positive affective state that rewards eating. However, in an early test of this idea, Van Vort and Smith [Physiol. Behav. 30 (1983) 279] reported that rats did not learn to prefer a food that was "real-fed" and satiating over a food that was "sham-fed" and not satiating. Subsequent investigators obtained similar findings with concentrated nutrient sources. With dilute nutrient sources, however, rats learned to prefer the real-fed to the sham-fed food. These and other findings demonstrate that nutrients have rewarding postingestive effects that enhance food preferences via a conditioning process. These reward effects appear separate from the satiating actions of nutrients, which may actually reduce food reward. Food intake and preference are controlled by a complex interaction of positive and negative signals generated by nutrients in the mouth and at postingestive sites.

Animals↗

Female rats show a bimodal preference response to the artificial sweetener sucralose.

The preference of female Sprague-Dawley rats for sucralose, a non-nutritive sweetener derived from sucrose, was evaluated in 23 h two-bottle tests with water or saccharin. Overall, the rats displayed weak or no preferences for sucralose (0.25-4 g/l) over water but strong preferences for saccharin (0.5-8 g/l) over water and saccharin (1 g/l) over sucralose (0.5 g/l). The rats also preferred a saccharin + sucrose mixture to sucrose, but sucrose to a sucralose + sucrose mixture. There were marked individual differences in sucralose preferences: about half the rats preferred sucralose to water at some concentrations while most remaining rats avoided sucralose. Both subgroups preferred saccharin to sucralose. Sucralose appears to have an aversive off-taste that reduces its palatability to rats.

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.

Animals↗

Selective effects of vagal deafferentation and celiac-superior mesenteric ganglionectomy on the reinforcing and satiating action of intestinal nutrients.

The role of vagal afferents and splanchnic fibers in nutrient-induced flavor conditioning and feeding suppression was determined. Male rats were fitted with intraduodenal (ID) catheters and given subdiaphragmatic vagal deafferentation (SDA), celiac-superior mesenteric ganglionectomy (CGX), combined (COM) treatments, or sham surgery. In separate conditioning trials, they were trained to drink (30 min/day) flavored saccharin solutions paired with concurrent ID infusions of 8% maltodextrin or water and 3.55% corn oil or water. Experiment 1 revealed that SDA and sham rats showed equal preferences for the nutrient-paired flavors over the water-paired flavors. In contrast, SDA rats, unlike sham rats, failed to suppress their intake of a palatable fluid when infused intraduodenally with maltodextrin or corn oil. Experiment 2 revealed that CGX, COM and sham rats all developed preferences for the maltodextrin-paired flavor, although CGX alone or COM attenuated the conditioned preference. CGX and COM treatments also attenuated or blocked the feeding inhibitory actions of ID nutrient infusions. These findings along with prior data indicate that gut vagal afferents and splanchnic nerves are not essential for flavor-nutrient preference conditioning, whereas both vagal afferents and splanchnic nerves are implicated in carbohydrate- and fat-induced satiation.

Afferent Pathways↗

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.

Animals↗

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.

Animals↗

Dopamine D1 and D2 antagonists reduce the acquisition and expression of flavor-preferences conditioned by fructose in rats.

The effects of dopamine (DA) D(1) and D(2) receptor antagonists on the acquisition and expression of flavor-preferences conditioned by the sweet taste of fructose were examined. Food-restricted rats were trained over eight alternating one-bottle sessions to drink an 8% fructose solution containing one novel flavor (CS+) and a less preferred 0.2% saccharin solution containing a different flavor (CS-). Three groups of rats were treated daily with either vehicle (control group), SCH23390 (200 nmol/kg; D(1) group), or raclopride (200 nmol/kg; D(2) group) during training. Additional groups of vehicle-treated rats had their daily training intakes matched to that of the D(1) and D(2) groups. Preferences were assessed in two-bottle tests with the CS+ and CS- flavors presented in 0.2% saccharin solutions following doses of 0, 50, 200, 400, or 800 nmol/kg of either D(1) or D(2) antagonists. The D(1) and D(2) groups, unlike the control and yoked-control groups, failed to display a significant CS+ preference in the two-bottle tests following vehicle treatment. In addition, treatment with SCH23390 prior to the two-bottle tests blocked the expression of the CS+ preference in the control groups. Pretest raclopride treatment attenuated the CS+ preference at some dose levels. Raclopride also attenuated the preference for fructose in rats given two-bottle training with the CS+/fructose (CS+/F) and CS-/saccharin (CS-/S) solutions. These findings indicate that D(1) and D(2) antagonists block flavor-preference conditioning by sweet taste and that D(1), and to a lesser extent D(2), receptor antagonists attenuate the expression of a previously acquired preference.

Animals↗

Flavor preferences conditioned by intragastric ethanol with limited access training.

In a prior study, ad libitum fed rats learned a strong preference (90%) for a flavored saccharin solution (conditioned stimulus, CS+) paired with concurrent intragastric (IG) infusions of 5% ethanol over another flavor (CS-) paired with water infusions in unlimited access sessions (22 h/day). The present study expanded the investigation of ethanol-conditioned preferences to limited access sessions (30 min/day). Experiment 1 revealed that ad lib or food-restricted rats failed to develop a CS+ preference using the same CS solutions (0.05% Kool-Aid+0.2% saccharin) and IG infusions that were effective with long-term training. Experiments 2 and 3 mimicked the parameters from a report of successful ethanol conditioning in deprived rats: ethanol (0.5 g/kg) or water was infused intragastrically 5 min before access to sweetened CS solutions flavored with HCl or NaCl. Rats learned to prefer the ethanol-paired CS+ when the flavors were mixed with 5% sucrose but not when mixed with 0.2% saccharin. Experiment 4 revealed that 5% sucrose solutions flavored with 0.25% Kool Aid also supported flavor preference conditioning by IG ethanol (0.5 g/kg). CS+ preferences were obtained in rats trained with ethanol infused 5 min before or concurrent with CS+ intake, but not in rats trained with ethanol infused 30 min before CS+ intake. These data confirm that flavor preferences can be conditioned by IG ethanol using a limited access procedure. However, in contrast to 22 h/day training, 30 min/day training requires more intense CS flavors and a nutritive sweetener. The preference reinforcing actions of ethanol may develop slowly and are thus most effective with long training sessions or when intense CS flavors are used in short training sessions.

Animals↗

High dietary fat promotes syndrome X in nonobese rats.

High fat, low carbohydrate diets are popularly advocated for weight loss and improvement in metabolic Syndrome X, a constellation of risk factors for type 2 diabetes mellitus and cardiovascular disease. The effects of an energy-restricted (to prevent weight gain in excess of normal growth) high fat (60% of energy), low carbohydrate (15%) diet were assessed in both lean rats and in rats previously rendered obese through ad libitum consumption of the same high fat diet. In obese rats, restriction of intake failed to improve impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia, although it lowered visceral fat mass, liver lipid content and in vitro insulin hypersecretion compared with rats continuing to consume the high fat diet ad libitum. In lean rats, restricted intake of the high fat diet impaired glucose tolerance and increased visceral fat mass and liver lipid content. These findings support the conclusion that, in the absence of weight loss, a high fat, low carbohydrate diet not only may be ineffective in decreasing risk factors for cardiovascular disease and type 2 diabetes but may promote the development of disease in previously lower risk, nonobese individuals.

Animals↗

Saccharin as a sugar surrogate revisited.

Two papers by George Collier are reviewed and replications and extensions of these data are presented. The first paper by Collier and Bolles (1968) reported the total caloric intake of rats during sucrose versus water preference tests. In addition, a paired comparison was made with each of a wide range of sucrose solutions. The latter experiment resulted in a re-thinking of "preference" in that it showed that although rats drank more of a middle range concentration, they always consumed more of the higher concentrations in paired comparison tests. Many other behavioral studies have confirmed that the rat's attraction to the taste of sucrose is a direct function of sucrose concentration. The second paper by Collier and Novell (1967) reported that saccharin was similar to sucrose in that intake increased and then decreased as concentration increased, although in direct choice tests, higher concentrations were preferred to lower ones except in one case. Subsequent studies using a wider range of saccharin concentrations and a variety of test measures revealed, however, that saccharin preference and acceptance decreases substantially as concentration exceeds 0.4% (19.5 mM). Furthermore, saccharin versus sucrose choice tests indicate that optimal saccharin solutions (0.2-0.4%) are "isopreferred" to only dilute sucrose solutions (2-4%). Thus, at best, saccharin is only a weak surrogate for sugar.

Animals↗

Flavor preferences conditioned by sucrose depend upon training and testing methods: two-bottle tests revisited.

In confirmation of prior work, rats given one-bottle training with flavored 5% and 30% sucrose solutions (CS5 and CS30) strongly preferred the CS5 when both flavors were presented in intermediate 17.5% sucrose solutions. The CS5 preference has been attributed to a conditioned satiety response to the CS30 flavor, but equal intakes of CS5 and CS30 in one-bottle tests did not support this view. To determine if sweetness differences between training and test solutions contributed to the CS5 preference, new rats were trained and tested with flavored 10% sucrose solutions. One flavor (CS5) was paired with matched intragastric (ig) water infusions (=net 5% solution) and another flavor (CS30) was paired with matched infusions of 50% sucrose (=net 30% solution) during one-bottle training. In two-bottle tests with both flavors paired with an intermediate infusion (25%=net 17.5%), the rats initially showed no overall preference for the CS5 or CS30. Following additional training, the rats significantly preferred the CS30 to the CS5. The intragastric data suggested that a change in sweet taste context between training and testing might have accounted for the strong CS5 preference obtained in the first experiment. This was confirmed in a third experiment in which rats were trained with flavored 5% and 30% sucrose solutions and then given two-bottle tests with both flavors presented either in 5% sucrose or 30% sucrose. Rats tested with 30% sucrose strongly preferred the CS5 flavor, whereas rats tested with 5% sucrose significantly preferred the CS30 flavor. Thus, the outcome of two-bottle flavor preference tests and presumably other tests of conditioned flavor reward may be greatly influenced by the solutions used in the tests. The impact of this variable may be greatest when the training solutions do not substantially differ in their net postingestive reinforcing actions. This appears to be the case with 5% and 30% sucrose solutions because the satiating effect of the concentrated solution tends to counteract its nutrient reinforcing action.

Animals↗

Ethanol flavor preference conditioned by intragastric carbohydrate in rats.

The unpalatable flavor of ethanol solutions greater than approximately 6% may limit their consumption by rats. We determined if ethanol flavor avoidance, like bitter or sour taste avoidance, can be reversed by intragastric (IG) carbohydrate conditioning. Ad lib fed rats drank 5% ethanol and a matched flavor (0.05% citric acid+0.5% maltodextrin, CM) on alternate days. For control rats, postingestive effects were equated: when they drank one solution they were infused IG with the other. Conditioned rats were also infused with 5% ethanol when they drank CM, but when they drank 5% ethanol they were infused with CM + 16% maltodextrin, a potent reward in flavor preference learning. In choice tests, only the conditioned rats preferred ethanol to CM; both groups preferred 5% ethanol to water. Conditioned rats but not controls preferred ethanol to water when the concentration was raised to 10%, and sustained their preference when the infusate carbohydrate was gradually removed. When ethanol concentration was gradually raised to 25%, ethanol preference declined from 48% to 30% in the control rats and from 84% to 50% in the conditioned rats. Thus, ethanol flavor avoidance can be reversed or reduced by postingestive nutritive conditioning, which may combine with the pharmacological effects of ethanol to produce the acquired appetite for the flavor of alcoholic beverages.

Animals↗

Flavor quality and ethanol concentration affect ethanol-conditioned flavor preferences.

A previous report showed that outbred rats acquired preferences for a sweetened conditioned stimulus (CS) flavor paired with intragastric ethanol. To evaluate the role of sweet taste in ethanol conditioning, this study compared training with sweetened and unsweetened flavors. In Experiment 1, nondeprived rats were trained to drink one flavored solution (CS+, e.g., grape) paired with intragastric infusion of 5% ethanol and another (CS-, e.g., cherry) paired with intragastric water on alternate days. The volume of ethanol solution infused was matched to the volume of flavored solution the rats consumed. The sweet group's flavors initially contained 0.2% saccharin, reduced to 0.1%, 0.05%, and 0% over days; the plain group's flavors were unsweetened. The sweet group drank more and self-infused more ethanol during training and its preference for the CS+ over the CS- (without saccharin) exceeded that of the plain group (75% versus 62%). Experiment 2 equated total ethanol intake in rats trained with two combinations of flavor quality and ethanol concentration. The Sweet5 group drank flavors with 0.2% saccharin throughout training and tests and received 5% ethanol when they drank CS+, while the Plain10 group drank unsweetened flavors and the CS+ was paired with 10% ethanol. Despite equal daily ethanol doses, the Sweet5 group strongly preferred the CS+ (89%) while the Plain10 group avoided it (31%). The two groups continued to show opposite CS+ preference profiles even when both were tested with sweet CS flavors and 10% ethanol infusions. Thus, sweet taste contributes to the development of ethanol-conditioned flavor preferences, and this effect is not explained by a simple enhancement of ethanol intake.

Alcohol Drinking↗

Naltrexone suppresses the late but not early licking response to a palatable sweet solution: opioid hedonic hypothesis reconsidered.

Opioid antagonists suppress the intake of sweet solutions, but typically have little effect on the initial rate of drinking. The lack of an early drug response was investigated in the present study because it questions the general idea that opioid antagonists reduce the hedonic response to sweets. The first experiment, which measured the rat's licking response to a sucrose+saccharin (S+s) solution, revealed that naltrexone suppressed S+s intake but not initial lick rates. Experiment 2A indicated that the drug's delayed behavioral effect was not due to the 10-min injection-test interval used. Increasing the interval to 20 min did not reduce the latency of drug action. Experiment 2B tested the idea that rats require several minutes to detect that naltrexone has reduced the hedonic value of the S+s solution. The S+s solution was presented either for 30 min without interruption or for 3 min followed, after a 6-min delay, by another 27-min access. In both test conditions, naltrexone did not suppress S+s licking until 7-9 min of drinking had occurred. However, the drug blocked an "appetizer effect"; a post-delay increase in licking rate produced by the split-session test procedure. Microstructure analysis indicated that in all cases, naltrexone reduced S+s licking by reducing the number of lick clusters rather than lick cluster size. In contrast to these drug effects, Experiment 2C showed that reducing the concentration of the S+s solution decreased initial lick rates. Together, these findings suggest that opioid antagonists do not affect all aspects of flavor hedonics, but may primarily alter the intake-maintaining action of palatable flavors.

Animals↗

Lateral hypothalamic lesions impair flavour-nutrient and flavour-toxin trace learning in rats.

Food-restricted rats with ibotenic acid lesions of the lateral hypothalamus (LHx) learned to prefer a flavour paired with concurrent intragastric (i.g.) infusions of maltodextrin, although their preference was weaker than that displayed by sham controls. Unlike controls, the LHx rats failed to acquire a flavour preference when the i.g. maltodextrin infusion was delayed by 15 min. The same rats learned to avoid flavours paired with i.g. lactose or lithium chloride over short delays (15-30 min), but were impaired, relative to controls, at a long conditioned-unconditioned stimuli delay (2 h). These data indicate that the LH is critical for the formation of flavour-postingestive consequence learning over a delay, particularly with nutrient reinforcement. Lateral hypothalamus lesions might specifically impair the processing of nutrient-generated unconditioned stimuli and, more generally, could interfere with the maintenance of flavour memories.

Animals↗

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.

Animals↗