Dietary modulation of oral amphetamine intake in rats

The interaction of sucrose availability and oral self-administration of amphetamine was examined in 23 male Sprague-Dawley rats. Fourteen rats were given a 0.075 mg/ml amphetamine sulfate solution as their sole source of fluid and 9 rats were given water. Feeding conditions were alternated between weeks with both granulated sucrose and chow available and weeks with only chow present. Rats drank significantly less of the amphetamine solution when consuming sucrose and chow than when eating chow alone. Sucrose intake had a slight effect on water intake. Rats drinking the amphetamine solution consumed significantly less food, gained significantly less weight, and were significantly less efficient at using calories for weight gain than rats drinking water. However, when given access to sucrose, rats drinking the amphetamine solution chose a significantly greater proportion of their daily caloric intake as sucrose (60%) than rats drinking water (42.5%). The present results demonstrate that 1) amphetamine intake alters nutrient choice and 2) that dietary variables can profoundly affect drug self-administration.     

Sucrose intake as a function of its cost and the cost of chow

The avid consumption of pure carbohydrate solutions, which often results in a distortion of nutrient balance, is generally presumed to be driven by their taste. In the first of two experiments, we examined the effect of consumption cost on rats' intake of three concentrations of sucrose solution (8%, 16%, and 32%) when a nutritionally complete chow was concurrently freely available. In the second experiment, we examined the intake of 24% sucrose solution and chow as the consumption costs of both were varied. Increasing the cost of sucrose resulted in a reduction in the percent calories taken from sucrose; the steepness of the decline in intake with price was inversely related to the sucrose concentration and to the cost of chow. Chow calories were substituted for relatively expensive sucrose calories. An increase in the cost of chow resulted in a reduction in the percent of calories taken from chow and a protein-poor diet. The cost of sucrose did not affect the slope of the chow intake curve, presumably because, despite its sweet taste, sucrose was not a substitute for the protein, fat, and micronutrients in chow. Total caloric intake was conserved in all cases.

Thus, the avid consumption of sucrose solution is curtailed when it is costly; but the degree of change in intake with cost depends on the cost of an alternative food. These results suggest that diet selection involves a comparison not only of the taste and post-ingestive consequences of available foods, but also of the cost of calories and nutrients in the foods. Selection appears to be guided first by caloric requirements and the relative cost of calories, then by nutrient requirements and the relative cost of nutrients, and finally by taste.     

Flavor-cued modulation of intake in rats: role of familiarity and impact on 24-h intake.

Following training with distinctively flavored nutritive solutions that differ in concentration and thus in caloric value, rats demonstrate flavor-postingestive consequence learning by preferentially consuming one of the flavors in two-bottle tests (both flavors in nutrient-identical solutions.) Experiment 1 investigated whether the relative familiarity of the flavor-nutrient combinations encountered in two-bottle tests contributes to the observed preference. One of the training concentrations (rather than the customary intermediate concentration) was used to present the flavors in testing; thus, one of the flavors was in a familiar context while the other was in an unfamiliar context. The results of two independent trials (rats trained with 1 and 5% sucrose; rats trained with 5 and 40% sucrose) confirmed that two-bottle test preference was not a preference for the familiar flavor-nutrient combination. Experiment 2 examined whether caloric expectancies based upon a previously learned flavor-postingestive consequence association would affect total daily intake. On alternating days, rats consumed 30 mL of dilute (5%) and concentrated (40%) sucrose, each distinctively flavored. When given 30 mL of 22.5% sucrose containing each of the flavors on separate test days, they ate less chow and thus fewer total calories over 24 h when given the flavor previously paired with concentrated sucrose. Experiment 3 replicated the design of Experiment 2 except that fat calories were used instead of sucrose; no significant adjustment of chow intake in extinction tests was noted, even when the number of fat calories used in training was increased (Experiment 4). Thus, rats did not exhibit flavor-cued modulation of chow intake when trained with fat, in contrast to responsivity to flavor cues when trained with sucrose. This differential responding to fat versus carbohydrate calories is consistent with previous observations, in a variety of paradigms, that modulation of caloric intake is less energetically appropriate when ingested foods are high in fat relative to high-carbohydrate foods.     

Differential effects of sucrose and fructose on dietary obesity in four mouse strains

We examined sugar-induced obesity in mouse strains polymorphic for Tas1r3, a gene that codes for the T1R3 sugar taste receptor. The T1R3 receptor in the FVB and B6 strains has a higher affinity for sugars than that in the AKR and 129P3 strains. In Experiment 1, mice had 40 days of access to lab chow plus water, sucrose (10 or 34%), or fructose (10 or 34%) solutions. The strains consumed more of the sucrose than isocaloric fructose solutions. The pattern of strain differences in caloric intake from the 10% sugar solutions was FVB > 129P3 = B6 > AKR; and that from the 34% sugar solutions was FVB > 129P3 > B6 ≥ AKR. Despite consuming more sugar calories, the FVB mice resisted obesity altogether. The AKR and 129P3 mice became obese exclusively on the 34% sucrose diet, while the B6 mice did so on the 34% sucrose and 34% fructose diets. In Experiment 2, we compared total caloric intake from diets containing chow versus chow plus 34% sucrose. All strains consumed between 11 and 25% more calories from the sucrose-supplemented diet. In Experiment 3, we compared the oral acceptability of the sucrose and fructose solutions, using lick tests. All strains licked more avidly for the 10% sucrose solutions. The results indicate that in mice (a) Tas1r3 genotype does not predict sugar-induced hyperphagia or obesity; (b) sucrose solutions stimulate higher daily intakes than isocaloric fructose solutions; and (c) susceptibility to sugar-induced obesity varies with strain, sugar concentration and sugar type.     

Somatic and metabolic responses of mature female rats with dietary obesity to dorsomedial hypothalamic lesions: Effects of diet palatability

Caloric intake, body weight, obesity status (Lee Index) and incorporation of U-14 C-glucose into liver and retroperitoneal fat pad glycogen and lipid were studied in mature female rats that had received bilateral lesions or sham-operations in the dorsomedial hypothalamic nuclei (DMN) after dietary obesity was well established. Their diet consisted of a high-fat-sucrose chow mix, chocolate chip cookies and a drinking fluid of 32% sucrose in tap water. Comparable groups of DMN lesioned rats (DMNL rats) and sham-operated controls were maintained on lab chow pellets and tap water. Prior to the hypothalamic operation, the animals on the high-caloric regimen consumed significantly more calories than the rats on lab chow and also attained commensurately higher body weights and obesity indices. The bulk of the calories consumed during this time was derived from the cookies. Following DMNL, the animals maintained on lab chow became hypophagic and had lower body weights than the sham-operated rats, as has been previously reported. In rats on the high-caloric regimen, DMNL resulted in hyperphagia in comparison to all other groups. The greatest percentage of the calories during this time was derived from the high-fat-sucrose chow mix and sugar water. Correspondingly, DMNL rats on the high-caloric regimen had higher body weights and obesity indices than all other groups. At sacrifice, both a diet and lesion effect were noted in an elevated incorporation of U 14-C glucose in both fat pad and liver lipid and glycogen. The data are interpreted to mean that (1) when a highly palatable, high-caloric diet is available, DMNL do not exert their usual hypophagic and weight-lowering effects; (2) DMNL and control rats show excessive caloric intake when both groups are fed a highly palatable, high-caloric diet in comparison to their chow-fed counterparts. However, DMNL rats fed high-caloric diet also consume significantly more than controls fed this diet; (3) This excessive caloric intake of the DMNL rats possibly predisposes these animals to exaggerated lipogenesis in liver and adipose tissue; (4) the sham-operated controls on the high-caloric regimen also show greater lipogenesis but at a level intermediate between the chow-fed controls and the DMNL rats on the high-caloric diet.     

Independent effects of diet palatability and fat content on bout size and daily intake in rats

Although considerable evidence attests to the hyperphagic effects of high-fat (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density, and postingestive effects) which promote overeating is still unclear. The present studies investigated the independent effects of diet palatability and macronutrient composition on intake using the self-regulated intragastric infusion paradigm. In Experiment 1, rats were infused with either HF or high-carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily intake than HC; lick pattern analysis revealed that HF produced larger but not more frequent bouts. Test solution was not related to intake, possibly due to the relatively modest palatability manipulation. Experiment 2 provided a more sensitive test: The palatability manipulation was strengthened and diet infusion made optional by provision of chow. HF again elicited larger bout size and total daily intake (diet+chow) than HC. Rats given the more palatable solution significantly increased intake (via larger bouts) and thus the amount of diet infused, but chow intake decreased such that total kilocalorie intake was not significantly related to solution palatability. The reliable observation that HF promoted larger bout size and greater total kilocalorie intake than HC provides additional evidence that fat sends weaker feedback signals relevant to controls of both satiation (suppression of ongoing eating, behaviorally manifest in meal size) and satiety (suppression of subsequent intake, reflected in total daily intake).     

Intraoral intake and taste reactivity responses elicited by sucrose and sodium chloride in chronic decerebrate rats

The oral stimulating effects of sucrose and sodium chloride (NaCl) were assessed in chronic decerebrate and pair-fed intact control rats by measuring both oral motor taste-reactivity responses and intraoral intake volume. Taste-reactivity responses were videotaped during the first minute of the intraoral taste infusion. The infusion continued until the taste solution was rejected from the mouth, and the intake volume was computed accordingly. The number of ingestive taste-reactivity responses and the volume of intraoral intake consumed by pair-fed control and decerebrate rats increased with increasing sucrose concentration. Sucrose intake increased as concentration increased to 0.1 M, then plateaued between 0.3, 1.3, and 2.0 M sucrose for both groups. For control rats, intraoral NaCl elicited an inverted U-shaped function for both taste-reactivity responses and intake. Taste-reactivity responses of chronic decerebrate rats varied with NaCl concentration. In contrast to control rats, intake of NaCl did not differ from that of water for decerebrate rats. These data indicate that caudal brain-stem mechanisms are sufficient to control sucrose intake but are not adequate for the concentration dependent intake of NaCl. Second, these data also indicate that it is possible for taste-elicited oral motor responses to be dissociated from intake. The different roles of taste and postingestive factors in sucrose and NaCl intake are discussed.     

Obesity by choice revisited: effects of food availability, flavor variety and nutrient composition on energy intake

Recent work suggested that the energy intake and weight gain of rats maintained on chow and 32% sucrose solution could be increased by simply offering more sources of sucrose [Tordoff M.G. Obesity by choice: the powerful influence of nutrient availability on nutrient intake. Am J Physiol 2002;282:R1536-R1539.]. In Experiment 1 this procedure was replicated but the effect was not: rats given one bottle of sucrose and five bottles of water consumed as much sucrose as those given five bottles of sucrose and one of water. Adding different flavors to the sucrose did not increase intakes further in Experiment 2. The relative potency of sucrose and other optional foods was studied in Experiment 3. Sucrose solution stimulated more overeating and weight gain than fat (vegetable shortening), and offering both sucrose and shortening did not generate further increases in energy intake. Finally, foods commonly used to produce overeating and weight gain were compared. Sucrose was less effective than a high-fat milk diet, and offering cookies in addition to the milk did not increase energy intake further. The nature of optional foods (nutrient composition and physical form) was markedly more important than the number of food sources available to the animals, and is a better contender as the reason for "obesity by choice".     

Dietary self-selection vs. complete diet: body weight gain and meal pattern in rats.

Food intake and body weight gain of male adult Wistar rats were examined in two groups of animals. One group (n = 14) was allowed to select its diet from separate sources of protein (casein, 3.1 kcal/g), fat (lard and sunflower oil, 7.9 kcal/g) and carbohydrate (CHO, starch and sucrose, 3.3 kcal/g). Another group (n = 10) received a nutritionally complete diet (3.3 kcal/g). After 2 weeks of adaptation to the diets, body weights and meal patterns were recorded for at least 4 days. The total caloric intake was nearly identical for the two groups of rats. Rats given dietary choice gained less weight over 4 days than rats fed chow and showed reduced feed efficiency. During the 24-h period, self-selecting rats consumed 20.8% of calories as proteins, 21% as fats and 58.2% as CHO. Self-selecting rats ate significantly less calories during the day than did rats given chow. The chow diet consisting of 17.3% calories as protein, 7.6% as fat and 75.1% as CHO. When comparing the self-selecting group nutrient intakes to those of chow-fed group it was observed that 24-h protein calorie intakes were identical in both groups. Fat intake was significantly higher and CHO reduced as compared to chow-fed rats. During the day, CHO intake was higher in self-selecting rats, and fat intake was not significantly reduced. During the night, protein and fat intakes were significantly higher in self-selecting rats, while CHO intake was significantly decreased, particularly in the last periods of the night.(ABSTRACT TRUNCATED AT 250 WORDS)     

Overeating,dietary selection patterns and sucrose intake in growing rats

Weanling rats were allowed access to food for either 5 hours or 24 hours per day. Within each food availability condition one group had access to a complete diet and one group had access to the complete diet and a 32% solution of sucrose. Caloric intake and rates of growth were considerably higher in the 24 hour access groups. The availability of sucrose led to a small (10–15%) but consistent elevation in caloric intake in the ad lib condition but did not influence growth in either food availability condition. Absolute levels of sucrose intake and the proportion of calories taken from the sucrose solution were consistently higher in the ad lib group and increased with increases in body size for both groups. Dilution of the chow component or the sucrose component of the diet did not alter dietary selection patterns in either food availability condition. It appears that access to a palatable carbohydrate solution can lead to overeating in the rat but these solutions do not induce the rat to select imbalanced diets that compromise growth.     

Effort as determinant of intake and patterns of drinking in the guinea pig

The influence of effort (FR size) and duration of access to the drinking tube on the Guinea pig's daily water intake and pattern of drinking was studied. As FR size increased there was a reduction in the number of drinking bouts and in the daily intake. The Guinea pig adjusted to the decline in the number of drinking bouts by increasing the amount of water consumed per bout and compensated for the reduction in total intake by increasing the efficiency of utilization of water. These non-deprived animals were able to maintain control growth rates except during the most demanding schedules. These findings are discussed in relation to the hypothesis that the motivation for appetetive behavior arises from constraints on free feeding and drinking.     

Fat substitutes promote weight gain in rats consuming high-fat diets

The use of food products designed to mimic the sensory properties of sweet and fat while providing fewer calories has been promoted as a method for reducing food intake and body weight. However, such products may interfere with a learned relationship between the sensory properties of food and the caloric consequences of consuming those foods. In the present experiment, we examined whether use of the fat substitute, olestra, affect energy balance by comparing the effects of consuming high-fat, high-calorie potato chips to the effects of consuming potato chips that sometimes signaled high calories (using high-fat potato chips) and that sometimes signaled lower calories (using nonfat potato chips manufactured with the fat substitute olestra). Food intake, body weight gain and adiposity were greater for rats that consumed both the high-calorie chips and the low-calorie chips with olestra compared to rats that consumed consuming only the high-calorie chips, but only if animals were also consuming a chow diet that was high in fat and calories. However, rats previously exposed to both the high- and low-calorie chips exhibited increased body weight gain, food intake and adiposity when they were subsequently provided with a high fat, high calorie chow diet suggesting that experience with the chips containing olestra affected the ability to predict high calories based on the sensory properties of fat. These results extend the generality of previous findings that interfering with a predictive relationship between sensory properties of foods and calories may contribute to dysregulation of energy balance, overweight and obesity.     

Regulation of NaCl solution intake and gastric emptying in adrenalectomized rats

Adrenalectomized (adrex) rats adaptively increase NaCl intake to compensate for the uncontrolled loss of Na(+) in urine due to the absence of aldosterone. After a period of NaCl deprivation, they ingest saline avidly but stop drinking before hyponatremia is repaired. The present experiments determined whether pre-systemic signals inhibit further NaCl intake, and whether gastric emptying of Na(+) is modulated according to the concentration of ingested NaCl solution. After overnight deprivation, adrex rats consumed 0.05 M and 0.15 M NaCl at a maximally fast rate ( approximately 1.7 ml/min) and emptied ingested fluid from the stomach at a slower but maximally fast rate ( approximately 1.1 ml/min). When 0.30 M NaCl was consumed instead, fluid intake still was maximally fast but gastric emptying slowed in proportion to concentration so that the emptying of Na(+) was comparable to that observed when 0.15 M NaCl was ingested ( approximately 0.13 meq/min). When 0.50 M NaCl was consumed, intake slowed proportionately so that Na(+) consumption was comparable to that observed when 0.30 M NaCl was ingested ( approximately 0.5 meq/min). NaCl intake appeared to be inhibited both by the concentration of saline emptied from the stomach and by the volume of ingested fluid in the stomach and small intestine. Gastric emptying also slowed proportionately when 0.50 M NaCl was consumed, as if the rats were regulating the delivery of Na(+) to the small intestine. These results suggest that adrex rats can detect the volume and concentration of ingested NaCl solution presystematically and integrate these two variables, and thereby modulate the rates of Na(+) intake and gastric emptying.     

A 5-HT2C agonist elicits hyperactivity and oral dyskinesia with hypophagia in rabbits

Serotonergic 5-HT2C and 5-HT1B receptors mediate inhibitory controls of eating. Questions have arisen about potential behavioral and neurological toxicity of drugs that stimulate the 2C site. We evaluated eating and other motor responses in male Dutch-belted rabbits after administration of m-chlorophenylpiperazine (mCPP). Studies conducted in vitro and in vivo assessed the pharmacological specificity of the ingestive actions of this agent. mCPP (0.15-10 micromol/kg sc) reduced consumption of chow and 20% sucrose solution with equal potencies (ED50 approximately equal 0.6 micromol/kg). In radioligand binding to rabbit cortex, mCPP displayed 15-fold higher affinity for 5-HT2C than for 5-HT1B receptors. The serotonin antagonist mesulergine (7000-fold selective for 5-HT2C) reversed the hypophagic action of mCPP, but the 5-HT1B/1D antagonist GR127,935 did not. GR127,935 (0.5 micromol/kg) did prevent hypophagia produced by the highly selective 5-HT1B/1D agonist GR46,611. Observational methods demonstrated that mCPP decreased the frequency of eating chow but increased other motor activities. When rabbits consumed sucrose, videoanalysis revealed that mCPP reduced total time licking and the duration of individual bouts, but not bout frequency or the actual rate of consumption. mCPP increased locomotor and other activities, and greatly increased vacuous oromotor stereotypies and tongue protrusions. Nonetheless, rabbits licked accurately at the spout for sucrose. When sucrose was infused intraorally through a cheek catheter, mCPP actually increased the peak amplitude and overall magnitude of jaw movements. We conclude that mCPP stimulates 5-HT2C receptors to reduce food intake in rabbits. This hypophagia involves disruption of appetitive components of eating and is accompanied by adverse motor actions. This profile raises questions about the use of the 5-HT2C receptor as a target for novel therapeutic agents for obesity.     

Flavor enhances the antidipsogenic effect of naloxone

Naloxone suppressed ingestion of tap water following a 15 hour deprivation at doses of 20, 10 and 5 mg/kg. Addition of saccharine (0.2%), saline (0.8%), sucrose (2%) and HCl (0.1 M) to tap water resulted in an increased sensitivity to naloxone-induced suppression of water intake following the 15 hour deprivation. The volume of quinine solution (0.1%) consumed was not altered by administration of naloxone. We suggest that naloxone suppresses drinking behavior due to alterations in taste perception.     

Effect of the dopamine D1-like receptor antagonist SCH 23390 on the microstructure of ingestive behaviour in water-deprived rats licking for water and NaCl solutions

The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on licking for sucrose, in particular the failure of the former to reduce bout size and the ability of the latter to induce a within-session decrement of bout number resembling either reward devaluation or neuroleptics on instrumental responding, we suggested that activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and its level is updated on the basis of a dopamine D2-like receptor-mediated reward evaluation. Consistent results were obtained in a study examining the effect of dopamine D2-like receptor antagonism in rats licking for NaCl solutions and water. In this study, we examined the effects of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40 μg/kg) on the microstructure of licking for water and sodium chloride solutions (0.075 M, 0.15 M, 0.3 M) in 12 h water deprived rats. Rats were exposed to each solution for 60 s either after the first lick or after 3 min that the animals were placed in the chambers. Bout size, but not bout number, was decreased at the highest NaCl concentration. SCH 23390 produced a decrease of bout number and of lick number mainly due to the decreased number of subjects engaging in licking behaviour, and failed to reduce bout size for Na Cl and water at a dose which increased the latency to the 1st lick but did not affect the intra-bout lick rate. In agreement with previous observations, these results suggest that dopamine D1-like receptors play an important role in the activation of reward-oriented responses.     

Liquid diet preference in weanling rats with dorsomedial hypothalamic lesions

Two groups of weanling rats received bilateral electrolytic lesions in the ventromedial and dorsomedial hypothalamic nuclei, respectively. Sham-operated animals served as controls. During 14 days post-operation, the intake of standard laboratory chow was measured. The rats then received, in addition to laboratory chow and tap water, a sweet, eggnog-type liquid diet for 17 days, during 14 of which food intake from both diets was measured daily. The liquid diet was then withdrawn and for two weeks laboratory chow was again the sole source of calories. During the availability of the liquid diet, both groups of rats with hypothalamic lesions profoundly reduced their intake of laboratory chow but conspicuously increased their consumption of liquid diet. The rats with dorsomedial lesions consumed as much liquid diet as the controls, while on laboratory chow alone they were highly significantly hypophagic compared with the controls. During the availability of the liquid diet the rats with dorsomedial lesions also became obese, but after the return to a period in which laboratory chow was the sole source of calories they lost this extra fat while again being hypophagic.It is suggested that the hypophagia observed in rats lesioned in the dorsomedial hypothalamic nucleus is not due to a deficiency in caloric metering but rather, alternatively, to (a) aversion to dry food, (b) taste preference for a sweet, liquid diet, (c) a motivational deficit or (d) a motor deficit.     

Control of protein intake in golden hamsters

Experiments were performed to investigate the behavioural responses of golden hamsters to manipulations of dietary protein availability. In the first experiment, hamsters were maintained on a protein-free diet and a powdered diet containing 64.8% protein (P64.8). When the P64.8 diet was progressively diluted with cornstarch, hamsters increased their intake of this diet fraction, but protein intake nevertheless declined. When the protein content of the diet was 16.2%, animals derived only 6% of total calories from protein and lost weight despite normal intake of calories. In the remaining experiments, hamsters were maintained on a self-selection regimen of high-protein chow, pure carbohydrate (sugar cubes), and pure fat (vegetable shortening). When high-protein chow was removed for either 5 or 10 days, total caloric intake and body weight declined, and hamsters selectively increased protein intake for several days after high-protein chow was returned. Hamsters allowed access to high-protein chow for only one hour each day markedly increased the amount of high-protein chow they ate during this hour as protein-restriction continued, but still consumed only about 10% of their normal daily protein intake on this schedule and lost 20% of starting body weight in two weeks; when free access to high-protein chow was restored, these animals selectively increased their protein intake above pre-restriction levels. Hamsters given access to high-protein chow only on alternate days demonstrated a relatively modest and slowly developing increase in protein intake, perhaps because they incurred only a moderate protein deficit. The results suggest that when protein intake falls below normal minimum requirements, hamsters will demonstrate an adaptive protein hunger but make only a limited adjustment to the dilution of a protein-containing diet fraction.     

Voluntary ethanol consumption and obesity in golden hamsters

Adult male golden hamsters with continuous access to Purina chow, water and either 15, 30 or 45% ethanol (v/v) for 14 weeks derived an average of 34, 37 and 22%, respectively, of their total calories from ethanol. Animals in the 15 and 45% ethanol groups derived up to 12.0 and 9.9 kcal/day, respectively, from ethanol, but the Purina chow intakes of these animals were such that their total caloric consumption and their body weights did not significantly exceed those of a control group having access only to Purina chow and water. In contrast, the 30% ethanol group derived up to 16.4 kcal/day from ethanol, and consistently consumed 25% more total calories than the control group, despite eating significantly less Purina chow. Furthermore, hamsters in the 30% ethanol group were 27% heavier and had significantly larger epididymal and retroperitoneal fat pads than controls. Similarities are noted between ethanol-induced obesity in hamsters and the dietary obesity which has been observed in rats having continuous access to Purina chow and a 32% sucrose solution.