Michael D. Kendig

Chronic restricted access to 10% sucrose solution in adolescent and young adult rats impairs spatial memory and alters sensitivity to outcome devaluation

Although increasing consumption of sugar drinks is recognized as a significant public health concern, little is known about (a) the cognitive effects resulting from sucrose consumption; and (b) whether the long-term effects of sucrose consumption are more pronounced for adolescents. This experiment directly compared performance on a task of spatial learning and memory (the Morris Water Maze) and sensitivity to outcome devaluation following 28 days of 2-h/day access to a 10% sucrose solution in adolescent and young-adult Wistar rats. Sucrose groups developed elevated fasting blood glucose levels after the diet intervention, despite drawing <15% of calories from sucrose and gaining no more weight than controls. In subsequent behavioral testing, sucrose groups were impaired on the Morris Water Maze, with some residual deficits in spatial memory observed more than 6 weeks after the end of sucrose exposure. Further, results from outcome devaluation testing indicated that in the older cohort of rats, those fed sucrose showed reduced sensitivity to devaluation of the outcome, suggestive of differences in instrumental learning following sucrose exposure. Data provide strong evidence that sucrose consumption can induce deficits in spatial cognition and reward-oriented behavior at levels that resemble patterns of sugar drink consumption in young people, and which can remain long after exposure.

Mephedrone in Adolescent Rats: Residual Memory Impairment and Acute but Not Lasting 5-HT Depletion

Mephedrone (4-methylmethcathinone, MMC) is a popular recreational drug, yet its potential harms are yet to be fully established. The current study examined the impact of single or repeated MMC exposure on various neurochemical and behavioral measures in rats. In Experiment 1 male adolescent Wistar rats received single or repeated (once a day for 10 days) injections of MMC (30 mg/kg) or the comparator drug methamphetamine (METH, 2.5 mg/kg). Both MMC and METH caused robust hyperactivity in the 1 h following injection although this effect did not tend to sensitize with repeated treatment. Striatal dopamine (DA) levels were increased 1 h following either METH or MMC while striatal and hippocampal serotonin (5-HT) levels were decreased 1 h following MMC but not METH. MMC caused greater increases in 5-HT metabolism and greater reductions in DA metabolism in rats that had been previously exposed to MMC. Autoradiographic analysis showed no signs of neuroinflammation ([125I]CLINDE ligand used as a marker for translocator protein (TSPO) expression) with repeated exposure to either MMC or METH. In Experiment 2, rats received repeated MMC (7.5, 15 or 30 mg/kg once a day for 10 days) and were examined for residual behavioral effects following treatment. Repeated high (30 mg/kg) dose MMC produced impaired novel object recognition 5 weeks after drug treatment. However, no residual changes in 5-HT or DA tissue levels were observed at 7 weeks post-treatment. Overall these results show that MMC causes acute but not lasting changes in DA and 5-HT tissue concentrations. MMC can also cause long-term memory impairment. Future studies of cognitive function in MMC users are clearly warranted.

Cognitive and behavioural effects of sugar consumption in rodents. A review.

The pronounced global rise in sugar consumption in recent years has been driven largely by increased consumption of sugar-sweetened beverages. Although high sugar intakes are recognised to increase the risk of obesity and related metabolic disturbances, less is known about how sugar might also impair cognition and learned behaviour. This review considers the effects of sugar in rodents on measures of learning and memory, reward processing, anxiety and mood. The parallels between sugar consumption and addictive behaviours are also discussed. The available evidence clearly indicates that sugar consumption can induce cognitive dysfunction. Deficits have been found most consistently on tasks measuring spatial learning and memory. Younger animals appear to be particularly sensitive to the effects of sugar on reward processing, yet results vary according to what reward-related behaviour is assessed. Sugar does not appear to produce long-term effects on anxiety or mood. Importantly, cognitive impairments have been found when intake approximates levels of sugar consumption in people and without changes to weight gain. There remain several caveats when extrapolating from animal models to putative effects of sugar on cognitive function in people. These issues are discussed in conjunction with potential underlying neural mechanisms and directions for future research.

Sweetening yoghurt with glucose, but not with saccharin, promotes weight gain and increased fat pad mass in rats

The claim that non-nutritive sweeteners accelerate body weight gain by disrupting sweet-calorie associations was tested in two experiments using rats. The experiments were modelled on a key study from a series of experiments reporting greater body weight gain in rats fed yoghurt sweetened with saccharin than with glucose (Swithers & Davidson, 2008). Both of the current experiments likewise compared groups fed saccharin- or glucose-sweetened yoghurt in addition to chow and water, while Experiment 1 included a third group (Control) given unsweetened yoghurt. In Experiment 1, but not in Experiment 2, rats were initially exposed to both saccharin- and glucose-sweetened yoghurts to assess their relative palatability. We also tested whether the provision of an energy-dense sweet biscuit would augment any effects of saccharin on food intake and weight gain, as seemingly predicted by Swithers and Davidson (2008). In Experiment 1 there were no differences in body weight gain or fat pad mass between the Saccharin and Control group, whereas the Glucose group was the heaviest by the final 5 weeks and at cull had the largest fat pads. Greater acceptance of saccharin predicted more weight gain over the whole experiment. Consistent with past reports, fasting blood glucose and insulin measures did not differ between the Saccharin and Control groups, but suggested some impairment of insulin sensitivity in the Glucose group. Experiment 2 found similar effects of glucose on fat mass, but not on body weight gain. In summary, adding saccharin had no detectable effects on body-weight regulation, whereas the effects of glucose on fat pad mass were consistent with previous studies reporting more harmful effects of sugars compared to non-nutritive sweeteners.

Metabolic Effects of Access to Sucrose Drink in Female Rats and Transmission of Some Effects to Their Offspring

The aims of this study were, first, to examine the metabolic consequences for female rats of having unrestricted access to 10% sucrose solution and, second, to test for effects of this dietary intervention on their offspring. In Stage 1 females were mated following a 4-week period in which one group was given the sucrose in addition to their normal chow and a control group was given chow and water only. Sucrose was removed at parturition and the pups monitored until weaning. Despite the development of glucose intolerance in sucrose-fed mothers, no effects were detected on litter size or pup weights. In Stage 2 voluntary activity of offspring was assessed over postnatal days (PND) 51-60 and their glucose tolerance measured at PND89-94. Again no effect of maternal diet was detected. Only male offspring were used in Stage 3, which began when they were 13 weeks old. Four groups were given 10% sucrose solution for 48 days in a 2 x 2 design, in which one factor was maternal diet and the other was whether they were given 2-h access to an activity wheel on alternate days. Higher fasting glucose levels were found in offspring of sugar-fed mothers. Exercise increased insulin sensitivity in these rats but not in offspring of control mothers. Behavioural measures of memory in Stage 3 did not reveal any effects of maternal diet or exercise. Overall, this study suggested that, while providing 10% sucrose solution ad-libitum was sufficient to impair maternal metabolism, the impact of this dietary manipulation on offspring may be revealed only when the offspring’s diet is similarly manipulated.

Persisting adiposity following chronic consumption of 10% sucrose solution: Strain differences and behavioural effects

The metabolic consequences of providing rats with extended access to sugar solutions have varied across studies. The two experiments in this study examined the effects of 8 weeks of 24-h access to 10% sucrose solution on adult Wistar rats. This was followed by 6 weeks of food restriction with no access to sucrose during which the behavioural effects of prior sucrose consumption on reward-oriented behaviour (Experiment 1) and reversal learning (Experiment 2) were assessed. In a comparison between rat strains, Experiment 1 found that sucrose accelerated weight gain in Albino but not Hooded Wistar rats, while sucrose-fed rats of both strains exhibited elevated fasting blood glucose and resistance to insulin. Importantly, at cull retroperitoneal fat deposits were elevated in sucrose-fed rats, at which point glucose and insulin had resolved to control levels and liver triglyceride content did not differ between groups. Experiment 2 also found that retroperitoneal fat content was higher in sucrose-fed rats at cull, after 6 weeks of behavioural testing without sucrose and with restricted access to food, and found a similar effect for epididymal fat. Behavioural testing in Experiment 1 found that sucrose exposure had no effect on habit formation assessed using an outcome devaluation paradigm. However, instrumental responding by sucrose-fed Albino rats was the least affected by pre-feeding, indicating a relationship between sucrose-induced obesity and food-seeking behaviour. In Experiment 2, sucrose-fed and control rats did not differ on a discrimination reversal task. In conclusion, this study demonstrates that the behavioural and metabolic effects of sucrose consumption vary with strain. Further, results indicate that sucrose consumption can lead to lasting increases in adipose tissue stores, a finding which has significant implications for human diets.

Individual differences in saccharin acceptance predict rats' food intake

Following previous results indicating that low acceptance of saccharin-sweetened yoghurt was associated with slower weight gain, the aim of this experiment was to determine which of three measures of individual differences would predict subsequent chow consumption, body weight gain, and fat mass. Pre-test measures consisted of amount of running in an activity wheel, amount of 0.1% saccharin solution consumed over 24h, and performance on an elevated plus maze (EPM). Rats were then maintained for three weeks on a diet of standard chow and water. Subsequent post-testing repeated the procedures used in pre-testing. The rats were then culled and fat pads excised and weighed. Pre-testing revealed a negative correlation between saccharin acceptance and activity, while neither measure correlated with anxiety in the EPM. Pre-test saccharin acceptance was positively correlated with subsequent chow consumption, percent weight gain, and g/kg fat mass. Multiple regression analyses including all three pre-test measures confirmed saccharin acceptance as a predictor of chow consumption and, marginally, of fat pad mass, while high anxiety predicted low percent body weight gain.

Contexts Paired with Junk Food Impair Goal-Directed Behavior in Rats: Implications for Decision Making in Obesogenic Environments

The high prevalence of obesity and related metabolic diseases calls for greater understanding of the factors that drive excess energy intake. Calorie-dense palatable foods are readily available and often are paired with highly salient environmental cues. These cues can trigger food-seeking and consumption in the absence of hunger. Here we examined the effects of palatable food-paired environmental cues on control of instrumental food-seeking behavior. In Experiment 1, adult male rats received exposures to one context containing three “junk” foods (JFs context) and another containing chow (Chow context). Next, rats were food-deprived and trained to perform instrumental responses (lever-press) for two novel food rewards in a third, distinct context. Contextual influences on flexible control of food-seeking behavior were then assessed by outcome devaluation tests held in the JF, chow and training contexts. Devaluation was achieved using specific satiety and test order was counterbalanced. Rats exhibited goal-directed control over behavior when tested in the training and chow-paired contexts. Notably, performance was habitual (insensitive to devaluation) when tested in the JF context. In Experiment 2 we tested whether the impairment found in the JF context could be ameliorated by the presentation of a discrete auditory cue paired with the chow context, relative to a second cue paired with the JF context. Consistent with the results of Experiment 1, the devaluation effect was not significant when rats were tested in the JF context with the JF cue. However, presenting the chow cue increased the impact of the devaluation treatment leading to a robust devaluation effect. Further tests confirmed that performance in the chow context was goal-directed and that sensory-specific satiety in the JF context was intact. These results show that environments paired with palatable foods can impair goal-directed control over food-seeking behavior, but that this deficit was improved by a cue paired with chow. This has promising implications for assisting individuals in controlling their eating behavior in environments designed to dysregulate it.

Peripheral nerve injury impairs the ability to maintain behavioural flexibility following acute stress in the rat

HighlightsPeripheral nerve injury does not impair instrumental learning.Peripheral nerve injury increases sensitivity to mild acute stress as measured by sensitivity to devaluation.Impairment caused by the combined nerve injury and mild acute stress is not proportioned to the level of painful sensory abnormalities. ABSTRACT Chronic neuropathic pain often leads to impaired cognition and reduced behavioural flexibility. This study used a rat model to investigate if a peripheral nerve injury, with or without an additional acute psychological stress, alters behavioural flexibility and goal directed behaviour as measured by sensitivity to devaluation. Neuropathic pain was induced by a chronic constriction injury (CCI) of the sciatic nerve. CCI, sham‐injury and naïve rats were trained to press two levers for two rewards. In outcome devaluation tests, one of the rewards was devalued by pre‐feeding it to satiety, immediately prior to an extinction test measuring responding on the two levers. The ability to preferentially direct responding toward the action earning the currently‐valued reward was taken as evidence of goal‐directed behaviour. To test the impact of acute stress, rats were subjected to 15 min restraint following pre‐feeding and prior to the devaluation test. Neither CCI surgery nor acute stress alone altered sensitivity to devaluation, but in combination CCI and acute stress significantly reduced sensitivity to devaluation. This Study demonstrates that relatively mild stressors that are without effect in uninjured populations can markedly impair cognition under conditions of chronic pain. It further suggests that overlapping neural substrates regulated by nerve injury and/or acute stress are having a cumulative effect on behavioural flexibility.

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.