Taste aversion learning during successive negative contrast.

Previous experiments found that acceptance of saccharin by rats was reduced if they had prior experience of sucrose or some other highly palatable solution. This study tested whether such successive negative contrast (SNC) effects involve acquisition of an aversion to the new taste. In three experiments, rats were switched from sucrose exposure in Stage 1 to a less palatable solution containing a new taste in Stage 2. In Experiments 1 and 2, a novel flavor was added to a saccharin solution at the start of Stage 2. In Experiment 1, preference tests revealed a weak aversion to the added vanilla flavor in the Suc-Sacch group, while in Experiment 2 an aversion was found in the Suc-Sacch group to the salty flavor that was used, compared with controls given access either saccharin or water in Stage 1. In Experiment 3, the Suc-Quin group, given quinine solution in Stage 2, displayed a greater aversion to quinine than a Water-Quin control group. These results support the suggestion that taste aversion learning plays a role in the initial suppression of intakes in a qualitative consummatory SNC effect. However, in the light of other evidence, it seems that the unusual persistence of successive negative contrast when rats are switched from sucrose to saccharin is not due to a long-lasting reduction in the value of saccharin.

Switching from sucrose to saccharin: Extended successive negative contrast is not maintained by hedonic changes.

Previous experiments found that acceptance of saccharin by rats was reduced if they had prior experience of sucrose or some other highly palatable solution. This reduction in saccharin consumption was particularly extended after a switch from sucrose. On the surface, this seems to correspond to a successive negative contrast (SNC) effect. This term was coined by C. F. Flaherty to describe the situation where consumption of a target solution is reduced by prior experience of a more valuable solution, typically a more concentrated version of the target solution. However, SNC effects are normally transient and assessed relative to a nonshifted control. Here, we confirm that the reduction in consumption seen when shifting from sucrose to saccharin is persistent and is seen relative to the traditional unshifted control. In addition, an analysis of licking microstructure showed that the shift from sucrose to saccharin suppressed the hedonic value of saccharin relative to controls, but this effect was less persistent than consumption suppression. Interestingly, a similar dissociation is observed in extinction of conditioned taste aversion (CTA): suppression of consumption produced by CTA is far more persistent than suppression of hedonic value. The comparison of results across procedures suggests that persistent SNC produced by a qualitative downshift from sucrose to saccharin appears different from quantitative downshifts in the concentration of a single solution, and qualitative downshift effects may involve CTA. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Switching from Sugar- to Artificially-Sweetened Beverages: A 12-Week Trial.

BACKGROUND: Consumption of sugar-sweetened beverages (SSBs) forms the primary source of added sugar intake and can increase the risk of metabolic disease. Evidence from studies in humans and rodents also indicates that consumption of SSBs can impair performance on cognitive tests, but that removing SSB access can ameliorate these effects. METHODS: The present study used an unblinded 3-group parallel design to assess the effects of a 12-week intervention in which young healthy adults (mean age = 22.85, SD = 3.89; mean BMI: 23.2, SD = 3.6) who regularly consumed SSBs were instructed to replace SSB intake with artificially-sweetened beverages (n = 28) or water (n = 25), or (c) to continue SSB intake (n = 27). RESULTS: No significant group differences were observed in short-term verbal memory on the Logical Memory test or the ratio of waist circumference to height (primary outcomes), nor in secondary measures of effect, impulsivity, adiposity, or glucose tolerance. One notable change was a significant reduction in liking for strong sucrose solutions in participants who switched to water. Switching from SSBs to 'diet' drinks or water had no detectable impact on cognitive or metabolic health over the relatively short time frame studied here. This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001004550; Universal Trial Number: U1111-1170-4543).

Unpredictability of access to a high fat/high sugar food can increase rats' intake.

When food is readily available, human self-imposed restrictions on consumption of palatable foods can lead to binge eating. Rodent models of human bingeing have produced increased intakes. However, access to highly palatable foods in such models has been largely predictable. The aim of the present study was to examine whether unpredictability of access might increase intakes in an animal model of bingeing, one in which rats had unrestricted access to chow and water throughout. Stage 1 of Experiment 1 gave female rats 2-h access to Oreos on either an unpredictable schedule or daily. In Stage 2 both groups were switched to predictable access on alternate days to test for persistent elevated intakes in the Unpredictable group. Although Oreo consumption did not differ between the two groups in Stage 1, the Unpredictable group ate more Oreos in Stage 2. In Stage 1 of Experiment 2 both groups were given access to Oreos every two days on average. The Predictable group was given alternate day access at a fixed time of day, whereas access days and times could not be predicted by the Unpredictable group. The latter was found to eat more Oreos in Stage 1, but this difference between the groups did not persist in Stage 2. Unpredictability did not appear to impact body weight gain in the study. In conclusion, this study indicates that unpredictability can increase consumption of palatable foods in addition to the increase produced by intermittent access.

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day.

RATIONALE: Daily limited access to palatable food or drink at a fixed time is commonly used in rodent models of bingeing. Under these conditions, entrainment may modulate intake patterns. Oxytocin is involved in circadian patterns of intake and, when administered peripherally, reduces sucrose intake. However, oxytocin's effects on intake under limited-access conditions and its potential interaction with entrainment have not been explored. OBJECTIVES: This study examined the role of entrainment on intake patterns, oxytocin's effects on sucrose intakes and locomotor activity and whether oxytocin's effects were mediated by its actions at the oxytocin receptor. METHODS: Sated rats received daily 1-h access to 10% sucrose solution either at a fixed or varied time of day. Rats received intraperitoneal oxytocin (0 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg) prior to sucrose access, and spontaneous locomotor activity was assessed in an open-field test. Rats were then pre-treated with an oxytocin receptor antagonist, L368,899, prior to oxytocin before sucrose access. RESULTS: Intake patterns did not differ between fixed- or varied-time presentations; rats consumed more sucrose solution in the middle as opposed to the early-dark phase. Oxytocin dose-dependently reduced sucrose intakes, but also reduced locomotor activity. There was some evidence of partial blockade of oxytocin-induced sucrose intake reductions by L368,899, but the results were unclear. CONCLUSIONS: Time of day and oxytocin impact sucrose solution intake under daily limited access in rats and the sedative-like effects of oxytocin should be considered in future studies on oxytocin and food intake.

Caffeine-based flavor preference conditioning in the rat.

The massive consumption of caffeine-containing beverages has prompted many studies involving human participants that have obtained caffeine-based increases in liking for a flavor. However, few studies have succeeded in obtaining caffeine-based flavor preference learning in rats. The main aim of the present study was to examine the conditions under which such learning can be detected. Three experiments differed mainly in terms of the base solution to which caffeine was added. Using a base of maltodextrin and saccharin, Experiment 1 found modest increases in flavor preferences in both food- and fluid-restricted rats. Experiment 2 found a strong caffeine-based flavor preference when water, but not saccharin, was used as the base. Whereas the first two experiments used a within-subject design, in which one flavor was paired with caffeine and a second flavor was not, Experiment 3 used a between-subject design with fluid-restricted rats given almond-flavored water containing caffeine in the Paired condition but not in the Unpaired condition; caffeine-based flavor preference learning was again found. In Experiments 1 and 2 post-conditioning exposure to the flavor alone produced a decrease in preference. In summary, the main achievements of this study were to extend the conditions under which caffeine-based flavor preferences can be detected in rats and demonstrate that such learned preferences are subject to extinction.

A systematic review and meta-analysis of animal models of binge eating - Part 1: Definitions and food/drink intake outcomes.

Binge eating involves consuming excessive amounts of food within a discrete period of time and is associated with significant impairments in binge-eating disorder and bulimia nervosa. While research on clinical binge eating has provided valuable aetiological insights, animal models allow for closer examination of environmental, biological, and developmental risk factors. Numerous animal models of binge eating exist and differ widely in operational definitions of bingeing, animal characteristics and methodological parameters. The current review aimed to synthesise the available published evidence on these models. A systematic review of binge definitions in 170 articles found most studies displayed good face validity. Meta-analyses on 150 articles confirmed that the amount of food or drink consumed by animals under binge conditions was larger than that of non-binge conditions across many protocols. The meta-regression revealed species, strain, and sex moderated binge effect size, with the largest effect observed in studies with female animals and mice. Risk of bias assessment identified that improved reporting of allocation, baseline characteristics and outcome assessment is required in future studies.

Sucrose-based flavor preferences in rats: Factors affecting detection of extinction.

Rats that have consumed a novel target flavor added to a sucrose solution will develop a preference for that flavor. Such preferences appear to persist over the course of many presentations of the flavor alone when animals are not food-deprived. However, previous research indicates that an extinction effect (a reduction in preference) can be obtained when training or testing is carried out in animals that are hungry. In a series of experiments that produced flavor preferences in hungry rats by adding the flavor to a sucrose solution, three (Experiments 1, 2A, 2B) established that the concentration of sucrose and the nature of the flavor influenced the results but failed to detect extinction. Two-bottle choice tests showed some loss of preference but this occurred both in subjects given the extinction treatment (flavor-only presentations) and in control subjects given just water. A loss of preference in rats given an extinction treatment as opposed to controls given only water was, however, found in Experiments 3 and 4. These experiments differed from Experiments 1 and 2 in that the extinction stage involved the presentation of two bottles containing the flavor, thus matching the two-bottle procedure used in the test phase. These results confirm that experiencing a flavor alone can result in extinction of a conditioned flavor preference in hungry rats but indicate that the effect is highly context-specific, requiring the conditions of the test to match those of the extinction procedure. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sex differences in recovery from cognitive and metabolic impairments induced by supplementary sucrose in rats.

Consumption of beverages containing around 10% sucrose contributes to worldwide obesity. Studies using rats can increase understanding of the consequences of such consumption. The present experiment aimed to compare male and female rats, first, in terms of cognitive and metabolic impairments produced by excessive intakes of 10% sucrose solution (Stage 1:8 weeks) and, second, with regard to recovery once access to sucrose ceased (Stage 2:4 weeks). All animals had unrestricted access to chow and water throughout. The primary cognitive outcome was performance on a place recognition task. The primary metabolic outcome was retroperitoneal fat pad mass/kg bodyweight at cull, with body weight and glucose tolerance as secondary outcomes. In a 3 × 2 between-subject factorial design the first factor was whether rats had: (1) unlimited access to a 10% sucrose solution and water throughout both stages (Suc-Suc); (2) were switched from sucrose in the 8-week Stage 1 to water only in the 4-week Stage 2 (Suc-Water); or (3) had no access to sucrose in either stage (Water-Water). The second factor was sex. A major metabolic outcome was that of persistent adiposity in both males and females in the Suc-Water condition. As for place recognition, females in the Suc-Suc condition showed greater long-term resistance than males to the impact of excessive sucrose on spatial memory impairment. Overall, few sex differences were found in secondary metabolic outcomes.

Time-of-day affects the amount rats run during daily sessions in activity wheels.

When rats are given daily sessions of access to activity wheels, the amount that they run can increase over sessions. In addition to the suggestion that this could indicate the development of an addiction, there are alternative explanations. The present study tested whether running at a fixed time of day (ToD) might allow stronger entrainment of circadian rhythms than running at varied ToDs. In two experiments, Fixed groups of male rats were given 90-min wheel sessions at a fixed ToD during their dark period, while such sessions for Varied groups were given at times that varied over days between early in or in the middle of the dark period. In addition, each experiment also contained inactive controls in order to assess running-induced changes in body weight. Daily wheel sessions were given for 12 days in Experiment 1 and for 18 days in Experiment 2 to younger rats. In Experiment 1 the Fixed groups ran more each day, whereas little increase was found in the Varied groups. In Experiment 2 this difference was found only for rats in the Fixed condition whose sessions were held in the middle of the dark period. Independent of condition, rats ran more in the middle than early in the dark period. As previously reported, the rats given wheel access consumed less food and gained less weight than inactive rats. In conclusion, the results provided support for the proposal that wheel sessions at a fixed ToD entrain circadian rhythms and thus facilitate increases in running.

Comparable metabolic effects of isocaloric sucrose and glucose solutions in rats.

Much of the global increase in sugar intake is attributable to rising consumption of sugar-sweetened beverages (SSBs). Because people compensate poorly for liquid calories, SSB consumption increases total energy intake, raising the risk of harmful metabolic effects in addition to possible effects of sugars per se. Glucose and fructose, the constituent sugars in sucrose, can exert distinct effects on metabolism and also differ in their satiating properties, suggesting that compensation for the calories in these sugars may also vary. In light of claims that the fructose within sucrose is particularly harmful, the present study compared the effects of giving rats access to either a sucrose or an isoenergetic glucose solution. Adult male rats were fed standard chow and water supplemented with 95 ml of 10% glucose (Glucose group; n = 10), 9% sucrose solution (Sucrose group; n = 10) or water only (Control group; n = 10) daily for 7 weeks. Sugar-fed groups had higher total energy intakes than the Control group, but the extent of this incomplete compensation did not vary between Sucrose and Glucose groups. In a short-term compensation test, sugar groups were less sensitive to the effects of a sweet pre-meal, with no differences between the Glucose and Sucrose groups. Relative to water, both sugars reduced insulin sensitivity after 4 weeks on the diets and elevated fat mass at 7 weeks. Results suggest that sucrose and glucose induce comparable metabolic impairments and alter the homeostatic regulation of food intake even under conditions where daily access is capped.

Sugar consumption and behavioural inhibition in the rat.

The metabolic effects of sugary drinks have been extensively studied, whereas the effects on psychological processes have received relatively limited attention. Several studies have found that high-sugar diets can produce impaired performance by rats on tests assessing spatial learning and memory. In contrast, despite claims that weakened inhibitory control underlies many sugar-induced deficits, evidence supporting this proposal has been limited. The aim of the present study was to assess the impact of high-sugar diets on response inhibition, as measured by rats' performance on a differential reinforcement of low rates schedule (DRL) in Experiments 1 and 2 and on a Pavlovian discrimination reversal task in Experiment 3. In all three experiments a 30-day diet stage, in which Sugar groups were given unrestricted access to 10% sucrose solution and Control groups had access to water only, was followed by behavioural tests. In Experiment 1 the Sugar group performed poorly on a spatial memory task, but no difference was detected between the performances of the two groups in the DRL test. In Experiment 2 longer DRL training was given and post-diet performance was assessed both before and after access to sugar was withdrawn. Null results were obtained under both conditions. In Experiment 3 rats' performance on a discrimination learned prior to the diet intervention was not affected by the high-sugar diet, but neither was performance once the discrimination was reversed. The implications of these results for understanding of sugar-induced psychological deficits are discussed.

Reduced acceptance of saccharin solutions by rats previously consuming more highly palatable solutions.

Rats first given 24-h access to 10% sucrose for 4 or 12 days (Stage 1) were then switched to a saccharin solution for a 12-day Stage 2. The initial result of this switch was that these Sucrose groups drank less saccharin than Water groups that had been given only water to drink in Stage 1. This difference was maintained throughout Stage 2 by the females that served in Experiments 1 and 4 and by the males that served in Experiment 3. Experiment 1 also found that access to 10% glucose in Stage 1 produced an essentially identical decrease in subsequent saccharin acceptance as that produced by giving 10% sucrose in Stage 1. The impact on subsequent acceptance of saccharin was also tested in rats given two types of maltodextrin solution. The first type of maltodextrin (Myopure brand) was used with the males in Experiment 2; this failed to find any difference between the Maltodextrin and the Water group. However, when a second type of maltodextrin (SolCarb brand) was given to males in Stage 1 of Experiment 3, the results for this group were similar to those from a group given sucrose in Stage 1. The final experiment confirmed that prior exposure to maltodextrin solutions can reduce saccharin acceptance by female rats. Overall, the results suggest that acceptance of saccharin is sensitive to a contrast effect, in that it is reduced by prior exposure to a solution that is more palatable but not necessarily sweet.

Bingeing in rats: Persistence of high intakes of palatable solutions induced by 1-day-in-4 intermittent access.

When animals are given access to a palatable food or drink on some days but not on others, the amount they consume can far exceed the daily amounts consumed by controls given daily access. A previous study demonstrated such bingeing when rats were given 4% sucrose solution. Importantly, it also found that, following 1-day-in-4 access for many weeks, intakes remained persistently higher than that of controls even when the conditions were changed to 1-day-in-2 access for both groups. One aim of the three experiments reported here was to test whether such persistent bingeing could be found for other solutions. This was confirmed in rats for a saccharin solution and a highly palatable saccharin-plus-glucose solution. When a maltodextrin solution was used, the 1-day-in-4 schedule initially produced higher intakes than controls given daily access. However, the difference between these groups was not maintained when both were switched to a 1-day-in-2 schedule. These results suggest that the hedonic value of a solution is more important than its caloric content in determining whether it will support persistent bingeing. A second aim was to test for evidence that the 1-day-in-4 procedure induced an addiction to the target solution. No such evidence was found using multiple measures including instrumental responding and anxiety-like behavior on the elevated plus-maze for craving and withdrawal respectively.

Situational relevance: Context as a factor in serial overshadowing of taste aversion learning.

In a serial overshadowing procedure, a target stimulus, A, is followed after an interval by a potentially interfering stimulus, B, and this is then followed by an unconditioned stimulus (US). An untested proposal from over four decades ago was that the degree to which B overshadows conditioning of A depends on whether or not the two events take place in the same context. To test this, two experiments used a 1-trial long-delay conditioned taste aversion (CTA) procedure: sucrose served as the target taste (A) and dilute hydrochloric acid (HCl) as the overshadowing taste (B), with lithium chloride injection providing the US. In Experiment 1, these tastes were novel: weaker overshadowing by HCl of an aversion to sucrose was found when the two tastes were presented in different contexts. Experiment 2 tested whether the effect of pre-exposure to HCl, thereby rendering it less effective in overshadowing a sucrose aversion, was also context dependent. In the conditioning session, rats again received either context-same or context-different presentations of sucrose and HCl. However, for some rats, HCl was pre-exposed in the same context to which it was later presented during conditioning (Consistent), while others were pre-exposed to HCl in a different context to the one in which it was presented during conditioning (Inconsistent). The Inconsistent group produced greater overshadowing than the Consistent group and thus confirmed that the latent inhibition effect was also context dependent. This study confirms the concept of situational relevance.

Motivation to run measured by progressive ratio tests: Failure to support the addiction hypothesis for rats.

When laboratory rats are given repeated access to an activity wheel, the amount that they run steadily increases. This suggests an analogy with drug dependency in animals and humans, in that this is marked by both increasing intakes of the drug and increasing motivation to obtain the drug (craving). This analogy was examined by measuring motivation to obtain an opportunity to run using a progressive ratio (PR) schedule, whereby the number of lever presses required to release a brake on an activity wheel was increased progressively. Each of two experiments included two groups of rats that differed in running experience. In Experiment 1, both groups were given 17 wheel-running sessions before they were given the PR test, with sessions for the short group lasting only 30 min, while those for the long group lasted 4.5 hrs. In Experiment 2, both groups were given 3-hr wheel sessions, with the short group given only four such sessions and the medium groups given 12 such sessions prior to their PR test. In both experiments, the PR tests revealed that motivation to run was greater when the rats had not had an opportunity to run for at least 24 hrs prior to the test than when they had run the previous day. However, neither experiment produced evidence that motivation to run increased with the amount of previous running. Given only limited support for the analogy between running and drug addiction, steady increases in running may instead reflect circadian adaptation and/or increases in fitness.

The effect of dose expectancies on caffeine withdrawal symptoms during tapered dose reduction.

BACKGROUND: Negative expectancies can exacerbate withdrawal symptoms via the nocebo effect. As such, information provided about dose reductions during attempts to taper a drug could contribute to withdrawal symptoms and increase the likelihood of relapse. The current study tested whether blinding participants to dose reductions during a supervised caffeine dose taper reduced these nocebo-induced withdrawal symptoms. METHODS: Three groups of moderate to heavy coffee drinkers had their dose of caffeine reduced (tapered) from 300 mg per day to 0 mg over the course of five days and reported withdrawal symptoms twice daily. Groups were given differing information about how much caffeine they were receiving. An Open Reduction group was given accurate information about dose reductions. A Blind Reduction group was given no dose information whatsoever. A Deceptive Reduction group was misinformed about dose, with instructions suggesting that the dose remained on 300 mg for three days then dropped to 0 mg. RESULTS: The Open Reduction group reported more pronounced caffeine withdrawal symptoms than the Deceptive Reduction group on the days with the greatest discrepancy between actual dose and informed dose, indicating a nocebo effect of open versus deceptive reductions. In addition, the rate of increase in reported withdrawal symptoms in the Blind Reduction and Deceptive Reduction groups was less than that of the Open Reduction group. CONCLUSION: These results suggest that awareness of dose reductions during a dose taper can result in a nocebo withdrawal effect, and that removing this awareness can reduce withdrawal. This has important implications for standard supervised dose-tapering practice, where patients are aware of the timing and magnitude of dose reductions.

Sodium saccharin can be more acceptable to rats than pure saccharin.

The artificial sweetener saccharin is available in several forms, including pure saccharin (S) and saccharin sodium salt hydrate (SSSH). Acceptance and preference relative to 2% sucrose for these two forms was assessed using both older female and young male rats. At the higher of two concentrations, ∼0.4%, SSSH was more acceptable and more greatly preferred over 2% sucrose than was a similar concentration of S, whereas little difference between the two forms was detected at the lower concentration, ∼0.1%. These results indicate the importance for researchers of care in choosing and reporting the form of saccharin they use.

Metabolic and cognitive improvement from switching to saccharin or water following chronic consumption by female rats of 10% sucrose solution.

High consumption of sugar-sweetened beverages (SSBs) is a risk factor for weight gain and metabolic disease. Whether this risk is reduced by switching to 'diet' beverages containing low-calorie sweeteners (LCS) is controversial. Two experiments modeled whether a switch from SSB to LCS beverages produced positive outcomes on behavioral and metabolic measures. Both experiments consisted of a Stage 1, in which adult female rats received unrestricted access to 10% sucrose solution in addition to chow and water for 4 (Experiment 1) or 8 weeks (Experiment 2). In Stage 2 rats were switched to either saccharin (Suc-Sacch) or water (Suc-Water) or remained on 10% sucrose (Suc-Suc) for a further 4 (Experiment 1) or 7 weeks (Experiment 2). Experiment 2 contained a fourth group that was maintained on water throughout (Water-Water). In both experiments energy intake and weight gain in Stage 2 was reduced for Suc-Sacch and Suc-Water groups relative to the Suc-Suc groups and at cull the Suc-Suc groups showed poorer insulin sensitivity and greater g/kg fat than Suc-Water and Suc-Sacch groups. In Experiment 2 short-term place recognition memory was impaired at the end of Stage 1 but recovered to a similar extent in the Suc-Water and Suc-Sacch groups; when the latter groups were compared with the Water-Water group, recovery was found to be essentially complete. A higher saccharin concentration in Experiment 2 than in Experiment 1 increased absolute amounts of saccharin ingested but intake solution volumes remained low. These results show that switching from sucrose to either water or saccharin produces equivalent improvements on both metabolic and cognitive measures.

Variety overcomes the specificity of cue-potentiated feeding in rats.

Cue-potentiated feeding (CPF) describes the stimulation of food consumption by cues that have become associated with food. Determining under what Conditions CPF occurs is important to better understand how exposure to food cues contributes to overeating. CPF is typically found to be specific: cues enhance consumption only of the food they have signaled. Further, previous research has focused largely on discrete cues rather than multimodal cues such as a feeding environment. The present experiments paired a "Plus" context with highly palatable food and a "Minus" context with no food or chow in adult female rats. Experiment 1 confirmed that the Plus context enhanced consumption of the paired food (Froot Loops) but not a different food (banana bread). Experiments 2 and 3 tested whether pairing a variety of foods with the Plus context would overcome this specificity. In Experiment 2 the Plus context either contained bland chow (Chow group), 1 (Single group), or 3 palatable foods (Variety group). The test food, Froot Loops, was familiar but never paired with the Plus context. The Variety group exhibited CPF by eating more Froot Loops in the Plus than in the Minus context, while Single and Chow groups ate equivalently in the 2 contexts. Experiment 3 replicated this effect when the Minus context contained chow during training and when a novel food was tested. These findings have important implications for overeating given that modern food environments are typified by variety and that food consumption often occurs outside the home. (PsycINFO Database Record