Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean rats from chow to a palatable diet.
ABSTRACT Rats exposed to an energy rich, cafeteria diet overeat and become obese. The present experiment examined the neural and behavioural effects of shifting obese rats from this diet to chow and lean rats from chow to the cafeteria diet. Two groups of male Sprague Dawley rats (n=24) were fed either highly palatable cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of each group (n=12) was then switched to the opposing diet while the remainder continued on their original diet. The effects of diet switch on the response to restraint stress were assessed and rats were euthanised nine days after diet reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls. Rats switched from chow to cafeteria diet (Ch-Caf) became hyperphagic and had increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf-Ch). Caf-Ch rats were hypophagic with significant reductions in white (16%) and brown (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared to rats remaining on the cafeteria diet (Caf-Caf). Caf-Caf rats had an elevated plasma corticosterone response to restraint stress compared to Ch-Caf rats indicating that acute but not chronic consumption of palatable cafeteria diet may protect against stress. Caf-Ch rats had increased corticotropin releasing hormone mRNA expression in the dorsal hypothalamus compared to Ch-Ch rats implying that removal of the palatable diet activated the HPA axis. The results were discussed in terms of the links between palatability of diet, obesity and stress.
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ABSTRACT: Introduction Purified high-fat diet (HFD) feeding causes deleterious metabolic and cognitive effects when compared with unrefined low-fat diets in rodent models. These effects are often attributed to the diet’s high content of fat, while less attention has been paid to other mechanisms associated with the diet’s highly refined state. Although the effects of HFD feeding on cognition have been explored, little is known about the impact of refined vs. unrefined food on cognition. We tested the hypothesis that a refined low-fat diet (LFD) increases body weight and adversely affects cognition relative to an unrefined diet. Materials and methods Rats were allowed ad libitum access to unrefined rodent chow (CON, LabDiets 5001) or a purified low-fat diet (REF, Research Diets D12450B) for 6 months, and body weight and performance on an instrumental lever pressing task were recorded. Results After six months on their respective diets, group REF gained significantly more weight than group CON. REF rats made significantly fewer lever presses, and exhibited dramatically lower breaking points than CON rats for sucrose and water reinforcement, indicating a chronic reduction of motivation for instrumental performance. Switching the rats’ diet for 9 days had no effect on these measures. Conclusions Diet-induced obesity produces a substantial deficit in motivated behavior in rats, independent of dietary fat content. This holds implications for an association between obesity and motivation. Specifically, behavioral traits comorbid with obesity, such as depression and fatigue , may be effects of obesity rather than contributing causes. To the degree that refined foods contribute to obesity, as demonstrated in our study, they may play a significant contributing role to other behavioral and cognitive disorders.Physiology & Behavior 01/2014; · 3.16 Impact Factor
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ABSTRACT: To extend preliminary studies on the effects on food intake of the combined use of cannabinoid (CB) 1 and glucagon-like peptide-1 (GLP-1) receptor agonists and antagonists, the effect of these drugs on the feeding behavior in rats maintained on a free-choice, high-carbohydrate diet was investigated over a longer period of time. Rats were fed a standard diet for 3 days and then fed with both the standard and the high-sucrose chow. After 4 days of the high-calorie diet, the following combination treatments were administered daily by an intraperitoneal injection for the next 3 days: 1 mg/kg AM 251 (a CB1 receptor antagonist) or 1 mg/kg WIN 55,212-2 (a CB1 receptor agonist) together with 3 µg/kg exendin-4 (Ex-4, a GLP-1 receptor agonist) or 160 µg/kg exendin (9-39) [Ex (9-39), a GLP-1 receptor antagonist]. The total daily caloric intake and body weight were significantly reduced in rats treated with Ex-4 and AM 251 or WIN 55,212-2 compared with either of the drugs injected alone and the saline-injected controls. Both drug combinations selectively inhibited ingestion of the high-sucrose chow. Although Ex (9-39) administration did not significantly affect food consumption, it resulted in a marked body weight gain, indicating that the GLP-1 receptor antagonist caused a positive energy balance. It is concluded that AM 251 or WIN 55,212-2 and Ex-4, injected together, exert additive, inhibitory effects on the consumption of high-sugar food.Behavioural pharmacology 02/2014; 25(1):53-60. · 2.85 Impact Factor
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ABSTRACT: Like people, rodents exposed to energy-rich foods over-eat and become overweight. Removal of this diet activates stress systems, which may explain why people have difficulty dieting. We exposed rats to energy-rich foods in order to identify changes in the brain induced by that diet and by its removal. Sprague Dawley rats were fed lab-chow or an energy-rich cafeteria diet (plus chow). Following six or 15 weeks, half of each group was switched to the opposing diet. Rats were culled 48-hours later. We measured fat mass, plasma hormones, and assessed brains for mRNA expression of several genes. Cafeteria-fed rats consumed more kilojoules, weighed more and had elevated leptin (plus reduced CORT at 15 weeks) relative to chow-fed rats. Fifteen weeks of cafeteria diet suppressed μ-opioid and CB1 receptor mRNA in the VTA, but elevated amygdala GR, and six weeks of cafeteria diet reduced BDNF, compared to chow-fed rats. Rats switched to the cafeteria diet ate similar amounts as rats maintained on the diet, and switching to cafeteria diet after 15 weeks reduced amygdala GR expression. Rats switched to chow ate less than rats maintained on chow, and switching to chow following 15 weeks of cafeteria diet increased hypothalamic CRH mRNA. Therefore, 15 weeks of cafeteria diet produced changes in brain regions implicated in reward processes. Switching these rats to chow activated the HPA axis, while switching chow-fed rats to the cafeteria diet decreased GR expression in the amygdala, a region associated with stress. These findings have implications for dieting in humans.Behavioural brain research 02/2014; · 3.22 Impact Factor