The relationship between saccharin and alcohol intake in rats.

Male rats were given daily sessions during which a palatable saccharin solution was available. Based on intakes averaged over 3 days, groups with low, intermediate, or high intake of saccharin were formed. These rats were then given daily sessions in which alcohol (2-8%) or water were available. Initially, sessions were conducted with rats on a food restriction schedule; in later sessions, food was available ad lib. When rats were food restricted, there were no differences among the groups in terms of alcohol or water intake. When the food restriction schedule was discontinued, alcohol intake in the intermediate and high saccharin intake groups was generally higher than that of the low saccharin group. On the final series of alcohol sessions, the high saccharin group consumed significantly more 2% and 6% alcohol than the low saccharin group. These results are consistent with reports which have found that rats selected for high or low alcohol intake have corresponding high and low intakes of saccharin.     

Patterns of ethanol and saccharin intake in P rats under limited-access conditions.

Patterns of drinking and responding for ethanol (EtOH) and saccharin (SACC) were examined in the alcohol-preferring P rat using various limited-access paradigms. Adult female P rats (n = 10-20) were given 2-h access to EtOH (10-13% v/v) and SACC (0.0125% g/v) concurrently each day, or each solution individually on alternate days. Total 2-h SACC intake was significantly greater than EtOH under both concurrent (12+/-2 vs. 7+/-0.8 ml, p<0.05) and alternate-day access (18+/-1.6 vs. 10+/-0.5 ml) conditions. Under both conditions, however, EtOH intake (over 55% of the total) in the first 15 min was significantly greater than that of SACC (<25% of total). In an operant paradigm, total responding for EtOH (124+/-29) and SACC (114+/-7) under 2-h alternate-day conditions did not differ, but 65% of total EtOH responding occurred during the first 20 min versus less than 45% for SACC (p<0.05). Increasing response requirements (FR-1 to FR-5) did not significantly alter the total number of EtOH reinforcements, but decreased the total number of SACC reinforcements by approximately 50% (p<0.05). Increasing the EtOH concentration from 15% to 35% decreased the number of reinforcements approximately 50% but did not decrease the estimated g/kg EtOH intake. Increasing the SACC concentration from 0.0125% to 0.05%, however, nearly doubled the number of reinforcements. The greater preference for EtOH versus SACC during the initial part of the access period, together with the maintenance of EtOH intake in g/kg when the response requirements and the EtOH concentration were increased, suggests that EtOH intake is motivated by pharmacological consequences. Therefore, different motivational factors appear to underlie EtOH and SACC intake of the P rat. Furthermore, the pattern of EtOH intake and responding displayed by the P rat may be the result of a "bout-" or "binge-" like loss of control under restricted EtOH access conditions.     

Nutrient intake and growth in preschool children. I, Comparison of energy intake and sources of energy with growth

This is the first UK study for 20 years to relate nutrient intake to growth in pre-school children. Between May 1988 and April 1990, 153 healthy children aged 2–5 years from Edinburgh were studied. A subset of 54 children were assessed twice, 12 months apart. Nutrient intake was determined by the 7-d weighed inventory method. Anthropometric measurements included height, weight and skinfold thickness. Data were grouped by age and gender.
Despite low group mean energy intakes of 80–85% of the current UK Estimated Average Requirement of energy (DoH, 1991), the children were apparently growing normally. Anthropometric measurements were within the normal range for age and no significant relationship was found between energy intake and rate of growth, suggesting that energy intake was adequate.
Considerable variation was found in the composition of diets. A highly significant negative correlation was found between the % energy from fat and the % energy from sugars and a significant positive correlation between total energy intake and fibre intake. However, as no relationship was found between energy intake and % energy from fat, sugars and starch, the composition of the diet did not apparently influence total energy intake.     

Ethanol withdrawal and proclivity are inversely related in rats selectively bred for differential saccharin intake.

Withdrawal severity and voluntary alcohol consumption are inversely related in rats and mice. The present study demonstrated this empirical relation and extended it in two ways. First, the rats were selectively bred for low (LoS) and high (HiS) saccharin intake, a phenotype that correlates positively with ethanol intake and inversely with emotional reactivity. Withdrawal has not yet been studied in these rats. Second, proclivity to consume ethanol was measured as conditioned preference for an ethanol-paired flavor. After 2 weeks of forced exposure to ethanol and a period of abstinence, LoS rats showed elevated acoustic startle; HiS rats did not (Exp. 1). When ethanol- and no-ethanol solutions were available freely during conditioning, both LoS and HiS rats preferred a flavor paired with 4% ethanol, but only HiS rats preferred a flavor paired with 10% ethanol (Exp. 2A); when exposure to the two solutions was controlled, all groups except LoS males preferred flavors paired with 4% or 10% ethanol (Exp. 2B). Thus, as predicted, withdrawal was more severe in the line with less ethanol proclivity (LoS). These results implicate basic associative and affective processes in individual differences in patterns of alcohol use.     

Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats

Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of ethanol and saccharin (SACC) deprivations on operant oral self-administration. Alcohol-preferring (P) rats were allowed to lever press concurrently self-administer ethanol (15% vol/vol) and SACC (0.0125% g/vol) for 8 weeks. Rats were then maintained on daily operant access (nondeprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of ethanol daily, or deprived of ethanol and given 2 ml of SACC daily. All groups were then given 2 weeks of daily operant access to ethanol and SACC, followed by an identical second deprivation period. P rats responded more for ethanol than SACC. All deprived groups increased responding on the ethanol lever, but not on the SACC lever. Daily consumption of 2 ml ethanol decreased the duration of the alcohol deprivation effect (ADE). Home cage access to 2 ml of SACC also decreased the ADE but to a lesser extent than access to ethanol. A second deprivation period further increased and prolonged the expression of an ADE. These results show ethanol is a more salient reinforcer than SACC. With concurrent access to ethanol and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both ethanol and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between ethanol and SACC in their CNS reinforcing effects.     

Drinking saccharin increases food intake and preference--II. Hydrational factors

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. In this paper, we examined whether these changes in feeding behavior were due to overhydration resulting from drinking hyposmotic saccharin solution. Consistent with this possibility, the short-term food intake of rats was increased by drinking hyposmotic 0.2% saccharin dissolved in water, unaffected by drinking isosmotic 0.9% NaCl, and decreased by drinking 0.2% saccharin dissolved in 0.9% NaCl. In addition, rats showed a sustained increase in saccharin-induced food intake after antidiuretic hormone treatment, which was designed to exacerbate their positive water balance. Less consistent with a hydrational explanation of saccharin-induced feeding was the finding that rats drinking only 2ml 0.2% saccharin solution increased food intake. Also, gastric intubation of similar volumes of water produced a small, transient increase in feeding behavior, which was apparent after the first intubation only and could not be preserved by adding water-contingent flavors to the food. Taken together, these results suggest that the hydrational effects of drinking hyposmotic saccharin solution contribute to, but cannot account for, the increase in food intake. Hydration had no observable influence on the acquisition of flavored food preference.     

Stimulation of the nicotine antiinflammatory pathway improves food intake and body composition in tumor-bearing rats

Inflammation contributes to the pathogenesis of cancer anorexia-cachexia syndrome. Nicotine administration reduces cytokine levels and mortality during sepsis. Therefore, nicotine administration may result in improved anorexia-cachexia. Sixteen male Fischer rats inoculated with MCA sarcoma were assigned to random injections of nicotine (NIC; 200 mg/kg BW/d) or saline (C). Food intake (FI), body weight, body composition, interleukin (IL)-1, IL-6 levels were evaluated. Data were analyzed via Student's t-test for paired and unpaired data and ANOVA. FI started declining 12 days after tumor inoculation both in C and NIC rats, but the decline was significantly attenuated by nicotine administration. At the end of the study, lean body mass wasting was more severe in C rats than in NIC rats (P<0.05), whereas a trend toward attenuation of fat mass depletion was observed. IL-1 circulating levels were significantly lower in NIC rats than in C rats (114±21 pg/mL vs. 190±35 pg/mL, respectively; P<0.01), whereas the reduction of IL-6 levels in NIC rats was only marginally not significant when compared to C rats (555±174 pg/mL vs. 721±160 pg/mL, respectively; P=0.06). Our data suggest that the nicotinic antiinflammatory pathway may represent an interesting and possibly effective therapy for anorexia-cachexia syndrome.     

Food dependence in rats selectively bred for low versus high saccharin intake. Implications for "food addiction"

The “food addiction” concept implies that proneness to drug dependence and to food dependence should covary. The latter was studied in low- (LoS) and high- (HiS) saccharin-consuming rats, who differ in drug self-administration (HiS > LoS) and withdrawal (LoS > HiS). Sugary food intake in the first 1-2 h was higher in HiS than LoS rats. Sugar intake predicted startle during abstinence only among LoS rats. These results may suggest bingeing-proneness in HiS rats and withdrawal-proneness among LoS rats. However, intake escalation and somatic withdrawal did not differ between lines. Further study with selectively bred rats, with attention to definitions and measures, is warranted.     

Suboptimal intake of magnesium in rats. Effects during growth and gestation

To investigate the interaction of magnesium depletion and source of protein and the effect of this interaction on growth, female weanling Sprague-Dawley rats were fed diets based on 20% casein or 20% soy protein isolate which contained eithe adequate (800 mg/kg) or suboptimal (200 mg/kg) levels of magnesium. The initial suboptimal level of approximately 100 mg/kg magnesium was increased to approximately 200 mg/kg magnesium on day 6 of the study. The nutritional stress of rapid growth resulted in clinical signs of deficiency including audiogenic seizures in the animals fed the casein diet which was low in magnesium. Some clinical manifestations of deficiency persisted through almost all of the 6-week growth period. The lower nutritional quality of soy protein isolate and/or the components of soy which depress mineral bioavailability resulted in a higher rate of alopecia and skin sores in the rats fed the soy low magnesium diet than in those fed the casein low magnesium one. Growth retardation in the magnesium deficient animals occurred during the post-weaning growth phase. Gestational weight gain was also depressed by low magnesium intake to a greater extent than has been previously reported in response to a mild magnesium restriction. Because of recent reports of suboptimal intakes of magnesium by humans, further research of combined effects of subacute magnesium deficiency and utilization of foods containing soy protein is needed.     

Cumulative dietary energy intake determines the onset of puberty in female rats

Laboratory animal diets for studies to determine the endocrine-disrupting potential of chemicals are under scrutiny because they can affect both assay control values and assay sensitivity. Although phytoestrogen content is important, we have previously shown that a phytoestrogen-rich diet and a phytoestrogen-free diet were equally uterotrophic to rats and advanced vaginal opening (VO) when compared with the standard diet RM1. Abolition of the effects by the gonadotrophin-releasing hormone antagonist Antarelix indicated that these effects were mediated through the hypothalamus-pituitary-reproductive organ axis. In the present study, we investigated the relationship between cumulative energy intake and sexual maturation in female rats. Infant formula (IF) at different concentrations and synthetic diets, with a wide range of metabolizable energy (ME) values, were used to modulate energy intake. Increasing energy intake was associated with an increase in uterine weight (absolute and adjusted for body weight) for both IF and the synthetic diets. In both cases, the increased uterine weight was directly proportional to energy intake. Body weight was unaffected by IF consumption but, in the case of the diets, was increased proportionally with energy consumption. Antarelix abolished the uterine weight increases with both formula and the diets, whereas body weight was unaffected. The mean day of VO was also advanced by high-ME diets and IF, whereas body weight at VO was unaffected. VO occurred at an energy intake of approximately 2,300 kJ/rat determined by measuring total food intake from weaning to VO, indicating that this cumulative energy intake was the trigger for puberty. ME is therefore a critical factor in the choice of diets for endocrine disruption studies.     

Acquisition of texture-cued fasting-anticipatory meal-size change in rats with adequate energy intake

To determine if an increase in intake at a meal before a long fast can be conditioned to food texture cues, male Sprague-Dawley rats were given a high- or low-fat diet in one texture (powder or pellet) for 1 h prior to a 12.5-h fast and in the other texture before a 3-h fast. Each group (N = 9) went through a pseudorandom sequence of four duplicates of each texture-fast pairing over 4 experimental days in each of three training trials, followed by one 4-day trial under extinction, i.e. without the difference in fast lengths between textures. Neither the high-fat group nor the low-fat group as a whole gave a clear indication of a learnt texture-cued increase in meal size before the longer fast relative to the shorter fast. However, the rats trained on the high-fat diet that had the highest intakes on the first 4 days of training showed a relative increase in the amount eaten of the texture predicting the longer fast during the third training trial, and this effect also approached statistical significance in the extinction test. These results provide some support for the conclusion that anticipatory hunger/satiety can be differentially conditioned to dietary texture cues, but only if sufficient food is eaten before a short fast to prevent the rise in hunger during longer fasts that reinforces the discriminative increase in meal size.     

Self-reported energy intake by FFQ compared with actual energy intake to maintain body weight in 516 adults

It is generally assumed that a FFQ is not suitable to estimate the absolute levels of individual energy intake. However, in epidemiological studies, reported nutrients by FFQ are often corrected for this intake. The objective of the present study was to assess how accurately participants report their energy intakes by FFQ. We compared reported energy intake with actual energy intake needed to maintain stable body weights during eleven controlled dietary trials. FFQ were developed to capture at least 90 % of energy intake. Participants, 342 women and 174 men, with a mean BMI of 22.8 (SD 3.1) kg/m2 filled out the FFQ just before the trials. Energy intakes during the trials were calculated from provided foods and reported free-food items, representing 90 and 10 % of energy intake, respectively. Mean reported energy intake was 97.5 (SD 12.7) % of actual energy intake during the trials; it was 98.9 (SD 15.2) % for women and 94.7 (SD 16.3) % for men (P = 0.004 for difference between sexes). Correlation coefficients between reported and actual energy intakes were 0.82 for all participants, 0.74 for women and 0.80 for men. Individual reported energy intake as a percentage of actual intake ranged from 56.3 to 159.6 % in women and from 43.8 to 151.0 % in men. In conclusion, the FFQ appeared to be accurate for estimating the mean level of energy intakes of these participants and for ranking them according to their intake. However, the large differences found on the individual level may affect the results of epidemiological studies in an unknown direction if nutrients are corrected for energy intakes reported by FFQ.     

Drinking saccharin increases food intake and preference--III. Sensory and associative factors

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. Here we describe experiments that examined whether these changes in feeding behavior were due to learning and/or the reinforcing sensory properties of saccharin solution. It was found that learning was unnecessary for the feeding response, as rats that drank saccharin increased food intake whether or not their food contained saccharin-contingent flavor cues. However, learning helped support and maintain the response, as rats repeatedly given flavored food together with saccharin to drink later increased intake when given the flavored food without saccharin (i.e. in extinction). The rewarding or hedonic effects of the immediate orosensory properties of saccharin were not responsible for its effects on feeding, as drinking saccharin before but not after eating flavored food increased food intake and food preference. Furthermore, hungry rats developed an aversion to flavored food paired with saccharin ingestion when the quantity of food was limited. This implies that the flavored food preference produced by drinking saccharin involves an association between sensory aspects of the food and the metabolic consequences of food ingestion, which interact with a postingestive action of drinking saccharin that is related to the rat's metabolic state.     

Drinking saccharin increases food intake and preference--I. Comparison with other drinks

To examine the orosensory and postingestive effects of saccharin solution on food intake and food preference, freely feeding rats were given flavored food to eat and a solution to drink for 2 h on eight to ten occasions. Relative to trials with a different flavored food and only water to drink, food intake was increased by drinking 0.2% saccharin or 0.45% NaCl, unaffected by drinking 1% almond extract, and decreased by drinking 10% glucose. Food preference, which was assessed in a choice test with simultaneous access to the two flavored foods, was increased by drinking 0.2% saccharin or 10% glucose and unaffected by drinking 1% almond extract or 0.45% NaCl. These results are consistent with the possibility that a combination of the oral and hydrational properties of saccharin solution increase food intake. Saccharin's sweet taste may be responsible for its effects on food preference.     

Adult female rats defend "appropriate" energy intake after adaptation to dietary energy

OBJECTIVE: To determine if adult female rats adapt to lower and higher dietary energy density. RESEARCH METHODS AND PROCEDURES: Study 1 compared high-fat (56%), high-energy density (HD) (21.6 kJ/g) and high-fat (56%), low-energy density (LD) (16.0 kJ/g) diets before surgery (two groups, 2 weeks, n = 16) and after surgery [ovariectomy (O) Sham (S); 2 x 2 factorial, n = 8; 6 weeks]. The second study (no surgery) compared high-fat (60.0%), high-energy (22.0 kJ/g) and low-fat (10.0%), low-energy (15.1 kJ/g) diets (n = 8). RESULTS: In study 1, food intake was similar for the first 2 weeks, but rats on the LD diet consumed less energy, gained less weight, and had lower nonfasted serum leptin (all p < 0.0001) than rats on the HD diet. After surgery, rats on the LD and HD diets had similar weight gain, but rats on the LD diet consumed more food (p < 0.0001) and less energy (p < 0.009). O rats consumed more food and gained more weight (p < 0.0001) than S rats. Results from study 2 were similar to those from study 1. DISCUSSION: The results demonstrated that O and S surgery rats and rats with no surgery adjust their food intake to defend a level of energy intake. This defense only occurred after a 2-week adaptation period. The major differences in final body weights and abdominal fat resulted from the initial 2 weeks before adaptation to energy density. Rats fed higher-energy diets seemed to "settle" at a higher level of adiposity, and rats fed lower-energy diets consumed more food to increase energy consumption.     

Exogenous recombinant human growth hormone effects during suboptimal energy and zinc intake

BACKGROUND: Energy and Zinc (Zn) deficiencies have been associated with nutritional related growth retardation as well as growth hormone (GH) resistance. In this study, the relationship between suboptimal energy and/or Zn intake and growth in rats and their response to immunoreactive exogenous recombinant human GH (GHi), was determined. RESULTS: Rats treated with GHi and fed ad-libitum energy and Zn (100/100) had increased IGFBP-3 (p < 0.05) as compared with NSS (215 +/- 23 vs. 185 +/- 17 ng/ml) along with similar body weight gain. Rats treated with GHi and fed suboptimal energy and full Zn (70/100) had significantly increased weight gain (109.0 +/- 18.2 vs. 73.8 +/- 11.0 g) and serum IGF-I levels (568 +/- 90 vs. 420 +/- 85 ng/ml), along with decreased total body water (TBW; 61.0 +/- 1.6 vs. 65.7 +/- 2.1%) as compared to NSS controls. However, body weight gain was reduced (p < 0.05) as compared with rats fed ad-libitum energy. Growth hormone treated rats fed only suboptimal Zn (100/70), had increased weight gain (217.5 +/- 13.2 vs. 191.6 +/- 17.9 g; p < 0.05) compared to those given NSS. These rats gained weight in similar amounts to those fed full Zn. Rats treated with GHi and fed both suboptimal energy and Zn (70/70) showed similar results to those fed suboptimal energy with appropriate Zn (70/100), along with significant increases in IGFBP-3 levels (322 +/- 28 vs. 93 +/- 28 ng/ml). All restricted rats had reduced 24-h EE (kcal/100 g BW) and physical activity index (oscillations/min/kg BW) and GHi did not overcome these effects. CONCLUSION: These results suggest that GHi enhances weight gain in rats with suboptimal energy and Zn intake but does not modify energy expenditure or physical activity index. Suboptimal Zn intake did not exacerbate the reduced growth or decrease in energy expenditure observed with energy restriction.