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The effects of neuropeptide Y (NPY) injected into the hypothalamic suprachiasmatic nucleus (SCN) or the lateral cerebral ventricle (LCV) at four different time points of the day on the subsequent 2h food intake from three macronutrient rich diets were examined. Adult Wistar male rats on 12-12 h light-dark cycles received either saline or NPY (lOOpmol) through chronically implanted guide cannulas into the SCN or the LCV. The results show that NPY was effective at stimulating energy intake from the dextrin/sucrose diet when injected in the SCN after lights-on, and total energy intake when injected in the LCV before and after lights-on. This suggests that NPY is effective at altering nychthemeral variations in total energy and energy from dextrin/sucrose diets, but this modulation is specific to the site of administration.

The present study tested the hypothesis that a saturated fatty acid (SFA)-rich diet is more obesogenic than diets with lower SFA content. In 8 female Sprague-Dawley rats fed a low-SFA canola or a moderate-SFA lard-rich diets at 67% of energy for 26 days, body weight gain, final body weight, obesity index, and food and energy intake were comparable. Twenty-nine rats were fed canola or high-SFA butter-rich diets (67% of energy) or chow for 50 days; then high-fat feeding was followed by ad libitum low-fat feeding (27% of energy) for 28 days and by a food-restricted low-fat diet for 32 days. High-fat feeding resulted in a greater body weight gain (P < .04), final body weight (P < .04), and energy intake (P < .008) in butter-fed rats than in canola- and chow-fed controls, after 26 or 50 days. Ad libitum canola and butter low-fat diets or chow feeding resulted in similar weight change, whereas food-restricted low-fat diets led to comparable weight loss and final weight. Canola-fed animals adjusted their intake based on diet energy density, whereas lard and butter-fed animals failed to do so. Abdominal fat (P = .012) and plasma leptin (P = .005) were higher in chow-fed controls than in canola-fed rats, but comparable with those of butter-fed rats. Prone and resistant phenotypes were detected with high-fat feeding. In conclusion, only feeding the high-SFA butter-rich diet led to obesity development and failure to adjust intake based on the energy density and preserving body fat even after weight loss. The high availability of SFA-rich foods in today's obesogenic environment could contribute to develop and maintain obesity.

Aminoglycosides (AG) such as gentamicin are antimicrobial drugs widely used in the hospital setting due to their efficacy in the treatment of severe gram-negative bacterial infections. However, all AG have the potential to cause nephrotoxicity. Two studies have been conducted (1) to assess the protein level of a diet that would give the best renal outcome with gentamicin administration, and (2) to get a better idea about the rhythms of food ingestion associated with the different protein levels. Adult female Sprague-Dawley rats fully adapted to a standard chow diet, the standard chow with 20% or 55% added casein were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns of rats were recorded every hour using a Diet Scan system and gentamicin nephrotoxicity indices were measured. The second study used rats that were fed the same diets and given a sham injection. Corticosterone was assayed to quantify the stress of the animals. Results showed that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and the 20% casein diet were found to be more protective against gentamicin-induced nephrotoxicity than the 55% casein diet. Therefore, while a protein-rich diet can be protective against gentamicin-induced nephrotoxicity, the present study demonstrates that a diet too high in protein might rather be harmful to the kidneys.

Feeding is organised within the 24-h of the light – dark (LD) cycle. Food is ingested in a circadian manner in nature and in laboratory animals kept under constant conditions. The circadian rhythmicity in food ingestion is driven by a biological clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The circadian organisation of food ingestion not only allows animals to live in harmony with their environment but food intake could also act as a zeitgeber for other rhythmic functions. Lesions in the area of the SCN result in the loss of most rhythmic functions as well as to a disrupted circadian rhythmicity of food and water intake. These findings, together with observations from daytime feeding experiments conducted in nocturnal animals, suggest that food intake may serve as a temporal signal for some peripheral organs to oscillate in phase with the SCN. This paper overviews and discusses how food intake interacts with the circadian system.

The prevalence of obesity among adults and children has increased steadily over the last few years worldwide, reaching epidemic proportions. Particularly alarming is the link between obesity and the development of chronic disorders such as heart disease, type 2 diabetes, hypertension and some cancers (Bjorntorp, 1997). Environmental causes of obesity are thought to include a sedentary lifestyle and an abundance of highly palatable energy-dense foods (Hillet al.2003). Genetic factors also contribute to susceptibility to obesity, although the genetic basis of most human obesities is thought to be polygenic (Comuzzie & Allison, 1998; Barshet al.2000). The present paper considers some of the animal models used to infer aspects of human obesity, with an emphasis upon their usefulness.

Sibutramine, a serotonin-noradrenaline reuptake inhibitor (SNRI), has been shown to be a safe and effective weight-loss drug. The purpose of the present study was to examine whether sibutramine has an effect on macronutrient selection in both female and male rats in addition to total food intake. Wistar rats of both sexes were divided into three groups, and each group was offered a different set of three sensorily contrasting macronutrient-specific diets, each set including carbohydrate-, protein-, and fat-rich diets. Sibutramine (10 mg/kg) was shown to consistently decrease carbohydrate and fat intake at all data points regardless of gender and diet. Intake of carbohydrate differed between male and female rats at 2 h post administration with 2.5 and 5 mg/kg of sibutramine. The effect of sibutramine on protein intake was diet- and gender-specific. All doses of sibutramine decreased total food intake regardless of gender and diet group beginning at 6 h post administration. In conclusion, sibutramine affected macronutrient selection and emphasis on dietary recommendations, as well as appropriate dosage according to gender should be considered during therapy.

Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal gland, is used to alleviate the symptoms of jetlag and treat sleeping problems. The objective of the present study was to examine the effects of a 7-h phase-shift from the natural peak of melatonin secretion on total food intake and macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided in three dietary groups, each group offered a simultaneous and different choice of a carbohydrate- and a protein-rich diet. Macronutrient intakes following intraperitoneal administration of four doses of melatonin (3000, 6000, 10 000 and 15 000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h postinjection) and long-term (12 h postinjection) nocturnal total food intake in both male and female rats, mainly with the two highest doses. This effect of melatonin was mainly due to a short-term increase of intake across all carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and across genders. This consistent effect of melatonin on the intake of carbohydrate-rich diets with contrasting sensory attributes rules out the possibility that melatonin acts on sensorymotor pathways, thus suggesting that melatonin's effect on food intake is controlled by the carbohydrate content of the diet. In contrast, melatonin could be affecting some sensory or motor processes peculiar to the ingestion of protein since it increased protein-rich diet intake inconsistently across the various preparations (casein, soy isolate, and egg protein) as well as genders. This evidence supports the view that melatonin acts as a time indicator, reinforcing the animals with a “night cue”, and favors predominant carbohydrate intake normally occurring at the beginning of the activity period.

Eating and drinking patterns were examined in intact and blinded adult male Sprague-Dawley rats fed a choice among isocaloric casein, sucrose/dextrin, and vegetable shortening/soybean oil diets. Weekly mean intake of all nutrients was altered in blinded rats, with increased lipid intake and decreased water intake in rats blinded for 2 weeks, lower carbohydrate but higher protein and water intakes in rats blinded for 4 weeks, while 2 weeks later blinded rats maintained high intakes of protein and water. The amplitudes of the daily rhythms for each nutrient behaved similarly to the weekly intakes. Delayed daily time of peak intake for all nutrients over successive weeks after blindness were found, indicating that the timing of peak intake free-runs. 24 h profile indicated time of day variations of nutrient intake tending to be less marked over successive weeks of blindness. Free-running animals maintained the link between carbohydrate intake and hypothalamus serotonin.

The objective of the present study was to look at the effect of a protein-rich diet on cyclosporine A (CsA)-induced acute nephrotoxicity in rodents using markers of tubular damage.Female Sprague-Dawley rats were conditioned to either a standard or a casein-rich diet for 2 weeks. Then, they were given CsA intraperitoneally (25 mg/kg/24 h or an equivalent volume of vehicle (Cremophor EL; Sigma Chemical Co, St. Louis, MO) for 7 days at 7 AM.During CsA treatment, bodyweight, caloric consumption, water intake, and urine output were not significantly different in animals fed with the standard Rat Chow and those on the high-protein feeding. On days 1 and 7, the 24-hour urine excretion of N-acetyl-beta-d-glucosaminidase (NAG) and beta-galactosidase (beta-GAL) were significantly (P.001) lower in CsA-treated rats on the high-protein diet than in those on the standard Rat Chow. After 7 days of treatment with CsA, no significant difference in the renal function level was found between rats fed with the standard or the casein-rich diet. The post-necrotic cellular regeneration in renal cortex was significantly lower (p0.001) in CsA-treated rats on the high-protein than on the standard diet. In CsA-treated rats on the standard diet, immunogold labeling showed a massive and specific concentration of the drug into lysosomes of proximal tubular cells. Contrastingly, no gold particle was found over the lysosomes of animals given the rich-protein feeding.In our current experimental conditions, a protective effect of high-casein diet against CsA-induced proximal tubular damage was observed in Sprague-Dawley rats.

Gentamicin-induced nephrotoxicity varies temporally, with a peak being observed when this antibiotic is administered during the resting period and a trough when given during the activity period of rats. These nychthemeral variations are modified by fasting and by restricted feeding schedules. In this study, food and water intakes of adult female Sprague-Dawley rats were measured during pretreatment (Days 1 to 5) and during treatment (Days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 or 0100h. A significantly higher level of serum creatinine was observed when gentamicin was administered at 1300 h compared to 0100 h, and a significantly lower creatinine clearance was found in rats treated with gentamicin at 1300 h compared to those treated with saline at the same time. Gentamicin treatment at 1300 or 0100 h resulted in a decrease in the 24-h food intake. In addition, in the gentamicin-treated group at 0100 h, the maximal food intake observed at late dark during the pretreatment period decreased during treatment, and early dark rather than late dark maximal intake occurred. Our data demonstrate that gentamicin induces a nephrotoxicity that varies temporally, and that gentamicin treatment inhibits food intake and alters its nocturnal variations.

To compare food and water intakes, adult male Wistar rats were infused during 7 days with serotonin (5-HT, 2.5 nmol/24 h) or artificial cerebrospinal fluid (CSF) in the suprachiasmatic nucleus (SCN) in a three-way selection of macronutrient-rich diets. Nocturnal energy intake from the casein-rich diet was significantly lower during infusion of 5-HT than before infusion. Decrease in nocturnal casein consumption was significant in the middle dark phase. Within the infusion period, water intake was reduced by 5-HT infusion during the early, middle and late light phase. The present results reinforce the hypothesis of a serotonergic control of water intake and provide evidence for SCN 5-HT involvement in casein-specific dietary selection.

To examine whether the diurnal rhythms of protein-rich and carbohydrate-rich diet ingestion can be altered by presenting the diets in different textural forms, adult male Wistar rats were assigned to two dietary groups. One group received a two-way choice between high-protein powder and high-carbohydrate granular (HPP-HCG) diets. In the other group the textures were reversed [high-protein granular and high-carbohydrate powder (HPG-HCP) diets]. Rats fed HPP-HCG diets selected significantly less protein (kcal) vs. rats fed HPG-HCP diets, during the 24-h and 12-h dark phase and during the 4-h early and late dark phases. Carbohydrate intakes of the two dietary groups were not significantly different. Total caloric intake for the HPG-HCP dietary group was significantly higher than that of the HPP-HCG dietary group during the 24-h and 12-h dark phase. Body weight was significantly lower in rats fed HPP-HCG diets. In conclusion, macronutrient-rich diets presented in different textural forms alter protein-rich diet ingestion and total energy intake.

Evidence for temporal variations in the nephrotoxicity of low doses of aminoglycosides were recently shown by using specific and sensitive parameters of renal toxicity. The aim of the present study was to evaluate the effect of a short period of fasting on the temporal variations in the renal toxicity of gentamicin. Twenty-eight normally fed (i.e., food and water were available ad libitum throughout the experiment) female Sprague-Dawley rats (weight, 175 to 220 g) and 28 fasted rats (i.e., only water was available during a 12-h fast before and a 24-h fast after gentamicin injection) were used. The animals were synchronized on a 14-h light, 10-h dark cycle (lights on at 0600 h) for 1 week before gentamicin administration. In July 1993, each group of animals was treated with a single intraperitoneal injection of saline (NaCl, 0.9%) or gentamicin (150 mg/kg of body weight) at either the peak (1400 h) or the trough (0200 h) of the previously determined toxicity. On day 1, the 24-h urinary excretion of beta-galactosidase, N-acetyl-beta-D-glucosaminidase, and gamma-glutamyltransferase was significantly higher in normally fed animals treated with gentamicin at 1400 h than in their time-matched controls and in normally fed animals treated at 0200 h (P < 0.01), which had normal levels of these enzymes. By contrast, the urinary excretion of these enzymes was significantly higher in both groups of gentamicin-treated, fasted rats than in their time-matched control groups (P < 0.01), reaching levels similar to those measured in normally fed rats treated at 1400 h. The accumulation of gentamicin was significantly lower in the renal cortex of normally fed rats treated at 0200 h than in rats treated at 1400 h (P < 0.05), but this time-dependent difference was not found in fasted rats treated at 0200 and 1400 h. Immunogold labeling done on ultrathin sections and observed by electron microscopy showed a similar subcellular localization of gentamicin in normally fed and fasted rats treated at either 1400 or 0200 h. These results suggest that the feeding period is of crucial importance in the temporal variations of the nephrotoxicity of gentamicin in rats.

Compared were the light-dark pattern of absolute energy intake and macronutrient selection of male Wistar rats intracerebroventricularly infused with glucagon (5 ng/h) or saline for 7 days in a three-way selection of macronutrients. Glucagon infusion induced a decrease in 24 h and nocturnal energy intake, whereas no significant change in kcal intake accompanied vehicle infusion. The decrease in kcal intake was due to a suppression of nocturnal ingestion of carbohydrate. This parameter was left unaffected with central vehicle infusion. Glucagon-infused rats had a significantly lower body weight gain than those infused with vehicle. Our study supports the hypothesis of central glucagon's suppressive effect on food intake, but reveals that the latter reflects a lower disposition to eat carbohydrate during the dark phase. The present work emphasizes the role of glucagon in the circadian regulation of carbohydrate intake.

This chapter aims to review literature on different aspects of obesity from fat-rich diets in non-human species. Usefulness of using small rodents in animal models to infer aspects of human obesity is discussed in terms of similarities and differences and how obesity is defined. The paradigm of using fat-rich diets in animal models of human obesity is explored according to its adequacy and dietary characteristics related to fatty acid composition. Physiological factors and mechanisms that can play a role in the development of obesity induced by a diet rich in fat are examined, namely the efficiency of nutrient utilization and the possible lack of inhibitory effect of fat on intake. The role of hormones such as leptin, ghrelin and insulin is discussed. Bevavioural mechanisms related to sensory-specific facilitation of eating with fat rich diets, altered feeding rhythmicity and learned eating are considered. The possible reversal of fat-rich diet induced obesity in animal models is explored. This chapter concludes with comments on appropriate design of animal studies and suggestions for future research.

Analyses of rats diurnal/nocturnal feeding behaviour were made according to the caloric density of the lipid ration. Adult male Sprague-Dawley rats were simultaneously offered three pure macronutrient diet rations: protein, carbohydrate, and lipid. The last was either kept isocaloric to protein and carbohydrate rations or was hypercaloric. Measurements of the food intake were recorded at 12-h intervals with respect to the dark phase and to the light phase of the circadian cycle (24h). Rats fed the hypercaloric lipid diet ration showed a significantly higher total energy intake compared with animals fed the isocaloric lipid diet ration. Also, in the hypercaloric group, the percentage of energy ingested as protein was significantly higher during both the light and dark phases, whereas the percentage of energy ingested as carbohydrate was significantly lower during the light phase and the 24-h cycle when compared with that of the isocaloric group. These results indicate that the caloric density of the lipid diet ration has differential effects on the diurnal/nocturnal energy intake and macronutrient choice and suggest that these feeding patterns may modify the outcome of experiments using macronutrient diet rations with different caloric density.

Epidemiological studies have shown a positive relationship between dietary fat intake and obesity. Since rats and mice show a similar relationship, they are considered an appropriate model for studying dietary obesity. The present paper describes the history of using high-fat diets to induce obesity in animals, aims to clarify the consequences of changing the amount and type of dietary fats on weight gain, body composition and adipose tissue cellularity, and explores the contribution of genetics and sex, as well as the biochemical basis and the roles of hormones such as leptin, insulin and ghrelin in animal models of dietary obesity. The major factors that contribute to dietary obesity – hyperphagia, energy density and post-ingestive effects of the dietary fat – are discussed. Other factors that affect dietary obesity including feeding rhythmicity, social factors and stress are highlighted. Finally, we comment on the reversibility of high-fat diet-induced obesity.

The effect of glucagon on macronutrient selection was studied using rats. Continuous infusion of glucagon (5 ng/μl/h) into the lateral cerebral ventricle increased total caloric intake and protein selection, and decreased carbohydrate selection. Continuous infusion of glucagon subcutaneously induced similar changes. Since a hyperglycemic response to the intracranial injection of 2-deoxy-D-glucose (2DG) disappeared in rats either with bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) (17) or with acquired (21) and congenital (10) blindness, and bilateral lesions of the SCN eliminated the hyperglucagonemic response to the 2DG-injection (19), changes in the plasma glucagon concentration after 2DG injection were examined in acquired and congenital blind rats. Consequently, it was found that the hyperglucagonemic response to 2DG was not observed in those blind rats which lacked the hyperglycemic response. In those SCN-lesioned and blind rats lacking the hyperglucagonemic response to 2DG, the protein selection was lower, and carbohydrate selection tended to be higher, than those selections found in the control rats. Considering the neural connection between the retina and the SCN, these findings suggest that glucagon may have a stimulatory effect on protein intake and a suppressive one for carbohydrate intake; and that the SCN may be involved in such a regulatory mechanism of feeding behavior through controlling the blood glucagon level.

Background/Aims: Isomaltulose (α-D-glucosylpyranosyl-1,6-D-fructofuranose) is a natural disaccharide used in human nutrition. It is structurally related to sucrose, but more slowly hydrolyzed and absorbed. Because this sugar’s metabolic effects are poorly characterized, we compared the effects of chronic ad libitum access to high-isomaltulose and high-sucrose diets on glucose metabolism in rats. Methods: Adult male rats were offered 62% isomaltulose, sucrose or starch diets ad libitum for 26 (trial 1) or 56 (trial 2) days. After 2- to 3-week adaptation, plasma glucose, fructose and insulin were measured after test meals of the adaptation diet. Results: The main finding was that both plasma glucose and plasma insulin concentrations were transiently but markedly increased after sucrose test meals compared to isomaltulose or starch meals. These differences were not associated with consistent differences in food intake, body weight gain or adiposity. Conclusions: Chronic isomaltulose feeding has beneficial effects on postprandial glucose metabolism in comparison to sucrose feeding in rats, although the effects are modest. Further work is warranted to determine whether substitution of isomaltulose for sucrose or other sweet carbohydrates might be therapeutically useful in patients with, or at risk for, insulin resistance or type 2 diabetes mellitus.

Relationships among feeding paradigm (single diet vs food selection) and arterio-venous differences (delta AV) of glucose, insulin and tryptophan were studied by measuring the temporal patterns of food intake and plasma parameters during 8 hr feeding cycles in rats. Adult male Sprague-Dawley rats were offered a single diet of fixed composition (20% casein) or a choice between two isocaloric diets (0% and 60% casein) for 2 weeks under 8-hr daily feeding conditions, food being offered during the dark cycle. Groups of animals were then killed at the beginning and at 2-hourly intervals throughout the feeding period. With both feeding paradigms, rats showed temporal patterns of energy, carbohydrate and protein intakes with a peak at the beginning and a trough at the end of the feeding period. However, in rats offered a dietary choice the intake of carbohydrate was significantly lower, and the intakes of energy and protein significantly higher than those found in rats offered a single diet. Throughout the feeding period, these differences between single and choice diets became less accentuated in the case of carbohydrate intake, but more accentuated for energy and protein intakes. Paradoxically, rats fed a choice of diets had a significantly lower weight gain than rats fed a single diet. The temporal variation of insulin secretion and tryptophan absorption varied inversely with the two diet paradigms. Moreover, in rats offered a choice of diets, macronutrient intake was significantly correlated with insulin secretion and venous glucose concentration. The opposed physiologic and metabolic responses to the feeding paradigms suggest the need for future studies to examine the possibility that such can function as synchronizers of biological rhythms.

Rats with ad libitum water and the ability to self-select among three macronutrient-rich diets--carbohydrate (CHO), protein (PRO), and lipid (LIP)--show a circadian rhythmicity in their ingestion. The aim of the present study was to determine whether this circadian rhythmicity is reliable from day to day. Eight rats were offered ad libitum water and a choice of three isoenergetic diet rations providing carbohydrate, protein, and lipid. Water and food intake was recorded every 3 h for 7 days. The reliability of the circadian rhythm of water and food intake was assessed by the Intraclass Correlation Coefficient (ICC) and the test-retest reliability using the Pearson's Correlation Coefficient (r). The results showed that the circadian rhythm of water, CHO, and PRO intake are strongly reliable. However, the circadian rhythm of LIP intake is less reproducible. Among the three reliable parameters-water, CHO, and PRO, the circadian rhythm of water intake was the most reproducible over 7 days. This suggests that water intake may be used as a marker of circadian rhythmicity in ingestive behavior.

The present study investigated the effect of single chow diet and two-way dietary choice between a protein-rich and a carbohydrate-rich diet ingested during free access or daytime access (08.00-16.00 h) on the rhythms of ingestion and on nocturnal levels of serum melatonin and pineal N-acetyltransferase activity in rats. Animals with free access to the single or the choice diets displayed a circadian rhythmicity of total food intake with peaks at the beginning, the middle and the end of the dark phase. Rats fed the dietary choice displayed a preference for carbohydrate at the beginning, and a preference for protein at the middle and the end of the dark phase. Under daytime feeding access, both dietary conditions resulted in only one peak of total intake at the beginning of the access period. Rats fed the choice diets on the daytime feeding schedule initially preferred carbohydrate to protein but this preference disappeared subsequently. Nocturnal peaks of serum melatonin and pineal NAT activity were lower with daytime access to dietary choice compared to ad libitum access. The results suggest that in a two-way selection of macronutrients, feeding cycle can directly act on the rhythms expressed within the pineal gland.

Previous studies have shown temporal variations in gentamicin-induced renal toxicity characterized by a peak when administered during the resting period and a trough during the active period. This time-dependent toxicity was also altered according to the macronutrient composition of dietary regimens offered to female rats. In the present study, adult female Sprague-Dawley rats were adapted to semipurified isocaloric diets containing 20% casein or soy-protein (10% fat each) or to a standard chow diet (18.1% mixed proteins; 4.5% fat). The animals were then chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day ip) or a saline solution administered in the middle of their resting period (1200 h) or in the middle of their activity period (0000 h). Body weights of rats injected in the middle of their resting period decreased over the last 6 days of gentamicin treatment. Total 12-h light and 12-h dark food intakes were decreased in gentamicin-treated rats. Rats fed the standard chow diet had significantly lower corticocellular regeneration, serum creatinine and blood urea nitrogen compared to those fed the casein- and soy-containing diets. The present study demonstrates that chronic gentamicin-induced renal toxicity varies temporally according to the time of administration and that a mixed protein diet containing a lower fat level can protect against gentamicin-induced nephrotoxicity.

The only evidence for nutrient selection comes from baseline or treatment effects on nutrient intakes that are qualitatively similar when sensorily contrasting forms of each macronutrient are investigated and/or dietary compositions and strains of rat or mouse are different within or between laboratories. By that criterion the only potential case of a treatment reliably altering macronutrient selection identified in the present review of the literature is d-norfenfluramine, fluoxetine and paraventricular serotonin (5-HT) reducing the intake of dextrin-containing diets at early dark. The only clear example of reverse effects of an agonist and an antagonist on dietary intake was found with serotonergic agents. Claims for catecholaminergic or opioid involvement in protein intake and peptidergic involvement in carbohydrate intake were not substantiated. There remain the issues of which learnt macronutrient-specific postgastric actions and sensory cues from the affected diet rely on the neural pathway(s) on which the drug is acting to alter dietary selection. Until experiments address these questions, the neural bases of nutrient-specific appetites will remain unknown. Drug effects must be consistent across differently textured and flavoured versions of each macronutrient tested.

Evidence for temporal variation in the nephrotoxicity of amphotericin B was recently reported in experimental animals. The role of food in these variations was determined by studying the effect of a short fasting period on the temporal variation in the renal toxicity of amphotericin B. Twenty-eight normally fed and 28 fasted female Sprague-Dawley rats were used. Food was available ad libitum to the fed rats, while the fasted animals were fasted 12 h before and 24 h after amphotericin B injection to minimize stress for the animals. Water was available ad libitum to both groups of rats, which were maintained on a 14-h light, 10-h dark regimen (light on at 0600 h). Renal toxicity was determined by comparing the levels of excretion of renal enzyme and the serum creatinine and blood urea nitrogen (BUN) levels at the time of the maximal (0700 h) or the minimal (1900 h) nephrotoxicity after the intraperitoneal administration of a single dose of dextrose (5%; control group) or amphotericin B (50 mg/kg of body weight; treated group) to the rats. The nephrotoxicities obtained after amphotericin B administration at both times of day were compared to the nephrotoxicities observed for time-matched controls. In fed animals, the 24-h urinary excretion of N -acetyl-β- d -glucosaminidase and β-galactosidase was significantly higher when amphotericin B was injected at 0700 and 1900 h. The excretion of these two enzymes was reduced significantly ( P < 0.05) in fasting rats, and this effect was larger at 0700 h ( P < 0.05) than at 1900 h. The serum creatinine level was also significantly higher ( P < 0.05) in fed animals treated at 0700 h than in fed animals treated at 1900 h. Fasting reduced significantly ( P < 0.05) the increase in the serum creatinine level, and this effect was larger in the animals treated at 0700 h. Similar data were obtained for BUN levels. Amphotericin B accumulation was significantly higher ( P < 0.05) in the renal cortexes of fed rats than in those of fasted animals, but there was no difference according to the time of injection. These results demonstrated that fasting reduces the nephrotoxicity of amphotericin B and that food availability is of crucial importance in the temporal variation in the renal toxicity of amphotericin B in rats.

Stress is associated with significant losses in the swine industry. Seasonal changes have been shown to affect stress resistance in several species of animals. In the present study, we examined the effect of two seasons (fall or winter) on plasma insulin, cortisol, and adrenocorticotrophin hormone (ACTH) levels from fasted normal and carrier pigs for stress susceptibility when submitted to a blood-sampling stressor between 10:00 and 11:00. Comparisons were made of 10 diurnally active normal (NN) and 8 carrier (Nn) pigs reared in the fall to 9 NN and 10 Nn pigs reared in the winter. The light-dark cycle throughout the period of the experiment was 10 h light/14 h dark, with lights on from 07:00 to 17:00. Feed consisted of the traditional western Canadian swine ration consumed ad libitum. Results revealed significant season-by-genotype interactions for plasma insulin and ACTH concentrations in response to the blood-sampling stressor. The normal pigs displayed a significantly lower plasma insulin level during winter compared to the fall season. Plasma ACTH of normal pigs was 18% lower in the winter compared to the fall season, although this difference was not statistically significant. The carrier genotype, on the other hand, demonstrated higher plasma insulin concentration and lower plasma ACTH concentration in the winter compared to the fall season. Furthermore, there was a main genotype effect in plasma cortisol concentration such that the carrier pigs experienced a greater level compared to the normal genotype. Similarly, the carrier pigs had a more acute ACTH response to the blood-sampling stressor compared to the normal pigs during the fall season. Results have demonstrated that these two seasons of the year affect the response of both genotypes to a blood-sampling stressor, with the carrier genotype experiencing a more intense stress reaction in the fall season. These results further contribute to the recent research indicating that carrier pigs for stress susceptibility have a unique stress response.

The effect of timing of gentamicin dosing relative to food access periods was evaluated in experimental animals. Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/kg of body weight/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h according to three food presentation schedules: food was available from 0800 to 1600 h in the first group, from 1600 to 0000 h in the second group, and from 0000 to 0800 h in the last group. Animals were thus subjected to a restricted feeding period. Results indicate that time-restricted feeding schedules displace the peak and the trough of gentamicin-induced renal toxicity, as evaluated by changes in the inhibition of sphingomyelinase activity, cellular regeneration (incorporation of [3H]thymidine into DNA of renal cortex), and blood urea nitrogen and serum creatinine levels, as well as histopathological lesions observed after 10 days of treatment. In fact, the toxicity was minimal when gentamicin was injected during the feeding period, while the maximal toxicity was found when gentamicin was administered during the fasting period. It is concluded that the feeding period can modulate aminoglycoside nephrotoxicity. The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephrotoxicity than the light-dark cycle.

Iron overload, with its associated toxic effects, has serious health consequences and results in damage to the liver, heart and other organs. Salicylate may be used as the lipophilic carrier, transporting more iron into hepatocytes. In this study, we examined the effect of the combined administration of these compounds on plasma lipid profile and lipoprotein composition, as well as on hepatic lipid concentration. Male Spraque-Dawley rats were injected i.p. with Fe (15 mg/kg weight). This injection was repeated 24 h later with a gavage of sodium salicylate (700 mg/kg). Control rats received 0.9% NaCl only. The peroxidation indices TBARS (P < 0.001) and conjugated dienes (P < 0.05) significantly increased in the blood (50 and 122%, respectively) and liver (333 and 101%, respectively) of Fe salicylate-treated rats. Concomitantly, blood and liver arachidonic acid content was diminished by iron treatment. In parallel, the plasma lipid profile was markedly affected in Fe-salicylate treated-rats. Lower plasma concentrations of total cholesterol (25%, P < 0.0001) cholesteryl ester, (34%, P < 0.001) and high-density lipoprotein-cholesterol (50%, P < 0.001) were observed. Lipoprotein composition analysis revealed enrichment of free cholesterol and depletion of cholesterol ester in very low-density, intermediate-density, low-density and high-density (HDL2, HDL3) lipoproteins. Furthermore, SDS-polyacrylamide gel electrophoresis revealed several alterations in the apolipoprotein distribution of these lipoproteins. The activity of lecithin:cholesterol acyltransferase was unchanged and could not account for the reduction of cholesterol esterification. As for the plasma, the liver exhibited a significant (P < 0.001) decrease in total cholesterol (2.42 +/- 0.07 versus 1.89 +/- 0.06 mg/g liver), essentially due to a reduction in cholesteryl ester (0.93 +/- 0.07 versus 0.51 +/- 0.03 mg/g, P < 0.001). Again, the activity of ACAT (dpm/mg microsomal protein) was not lower (12,700 +/- 1250) than that of controls (9650 +/- 1080). Thus, the iron-salicylate was able to induce peroxidation and to profoundly affect the intravascular and intrahepatic lipid, and plasma lipoprotein metabolism. Additional work is needed to elucidate the mechanisms involved in the underlying lipid and lipoprotein abnormalities.

The effects of short-term food deprivation on the serum and renal distribution and nephrotoxicity of tobramycin were studied in female Sprague-Dawley rats maintained on a 14-h light/10-h dark cycle (light on: 06:00). For the distribution study, a single injection of tobramycin (40 mg/kg, i.p.) was administered at 14:00 or 02:00 to normally fed animals or to animals fasted for 12 h before tobramycin injection; these treatment times correspond to the peak and trough of tobramycin nephrotoxicity as previously determined in other studies. The serum and cortical levels of tobramycin were significantly higher 60, 120, and 240 min after the injection in fasted animals treated at 02:00 compared with normally fed animals treated at the same time (p0.05). In animals injected at 14:00, similar levels of tobramycin were measured in both fasted and fed rats. In the nephrotoxicity study, female Sprague-Dawley rats were fasted for 12 h before and 24 h after the timed single injection of tobramycin (150 mg/kg, i.p.). The 24-h urinary excretion of beta-galactosidase was significantly higher in fasted animals treated at 02:00 than in fed rats treated at the same time of day. Seventy-two hours following tobramycin injection, serum creatinine levels and cortical levels of tobramycin were significantly higher in fasted rats treated at 14:00 than at 02:00 and in fed rats treated at 14:00. These data suggest that a short period of food deprivation modulates the temporal variations of tobramycin nephrotoxicity.

We investigated the effect of chronic infusion of neuropeptide Y (NPY) aimed at the hypothalamic suprachiasmatic nucleus (SCN) or the lateral cerebral ventricle (LCV) on food intake. The experiments were performed in adult male Wistar rats infused for 7 days with saline or NPY (10 and 100 pmol microliters-1 h-1) into the SCN (n = 18) or LCV (n = 17). Infusion of the lower dose of NPY in the SCN significantly decreased food intake, whereas infusion of the higher dose did not. There was no change in food intake specific to saline or either dose of NPY with infusion in the LCV. It is concluded that chronic infusion of NPY into the SCN at a dose of 10 pmol h-1 inhibits food intake in rats.

The aim of the study was to investigate the effect of different dietary carbohydrates such as corn starch, sucrose, fructose and glucose on carbohydrate and protein self-selection and on arterial and venous concentrations of glucose and insulin, and brain indoleamines in rats. Fructose and sucrose feeding induced the lowest food intakes which were due respectively to a lower carbohydrate and protein selection. The present data showed that feeding with dietary glucose as the main carbohydrate source gave the highest glycemic response, the lowest one being found with fructose and corn starch, and an intermediate one with sucrose feeding. The insulin response to the dietary carbohydrates followed a somewhat different pattern with the highest insulin secretion observed after fructose feeding whereas highly variable and inconsistent results were obtained following corn starch, sucrose and glucose feeding. Feeding chemically different sugars was also characterized by decreased serotonin synthesis in the raphe nuclei, brainstem and thalamus, and increased 5-HT synthesis in the hypothalamus of rats fed fructose when compared to glucose fed animals. The present results highlight the importance of considering the nature of dietary carbohydrates in the regulation of feeding.

Diet self-selection from carbohydrate, protein and lipid offered simultaneously was studied in adult male rats infused for 8 days with pyroglutamyl-CCK-8 (pGlu-CCK-8) (0.8 pmol/hr), a derivative of the COOH-terminal octapeptide of cholecystokinin (CCK), or vehicle bilaterally into the ventromedial hypothalamus (VMH). Infusion with pGlu-CCK-8 markedly decreased total daily energy intake mainly due to a suppressed carbohydrate intake. Both pGlu-CCK-8 and vehicle infusions caused a nonspecific decrease in protein intake, but the vehicle infusion caused a compensatory increase in lipid intake as well as carbohydrate intake, so their total energy intake was well maintained. These results suggest that the process of infusion into the VMH elicited itself a suppressive effect on protein intake, but that pGlu-CCK-8 infusion elicited a more specific suppressive effect on carbohydrate intake and, to a lesser extent, on lipid intake. These results also support the prediction that centrally administered CCK may suppress food intake and show in addition that such a suppression occurs selectively. The similarities and the differences in the patterns of macronutrient selection produced by vehicle of pGlu-CCK-8 infusions into the VMH provide further evidence of the unique functions of VMH and CCK in the feeding process.

Adult cats adapted to a semi-purified casein diet were used to study the effects of chronic doses of gluten or gliadin administered per os for 16 consecutive days, for a total of 700mg per kg per day, on various blood and brain parameters. The ad libitum food intake, serum amino acid content, brain, adrenal, and serum dopamine-β-hydroxylase activity, and cerebral GABAergic, cholinergic, dopaminergic, noradrenergic, and serotonergic metabolism of cats fed casein gluten or gliadin were studied. In the brain, the wheat proteins favored mesolimbic and nigrostriatal dopaminergic pathways and decreased the choline acetyltransferase and glutamic acid decarboxylase activities in these pathways thus suggesting an interaction between the corresponding neurotransmitters. The decreased food intake in cats fed gluten or gliadin was paralleled by an increased noradrenaline, dopamine, and serotonin contents in the brainstem areas. In treated cats the adrenal and serum dopamine-β-hydroxylase activities were decreased whereas this enzyme activity in the brain remained normal. The ratio of serum total tryptophan or tyrosine to the sum of six neutral amino acids were significantly decreased and inversely correlated with serotonin and catecholamine contents in the brain. Biochemical peripheral and cerebral disturbances observed following chronic gluten or gliadin administration could provide some basis for correlated behavioral properties of wheat peptides.

Adult cats were adapted to hypoglucidic semi-purified diets containing casein or soya as the protein source to study the effects of a 2 hr immobilization period. Body weight of cats fed hypoglucidic diets was significantly decreased. The control casein group showed higher plasma dopamine-β-hydroxylase activity but lower pyridoxal 5′-phosphate level than control soya group. Cats fed hypoglucidic casein diet, plasma glucose, insulin and pyridoxal 5′-phosphate levels were increased whereas cats fed hypoglucidic soya diet, pyridoxal 5′-phosphate levels were decreased and dopamine-β-hydroxylase activity increased when data were compared to their respective control groups. A 2 hr immobilization period induced hyperglycemia in all groups whereas cats fed soya diets, plasma insulin level and dopamine-β-hydroxylase activity were significantly increased and pyridoxal 5′-phosphate content significantly decreased. These results demonstrate that dietary casein and soya protein might be differentiated on a physiological basis and immobilization emphasized the biochemical disturbances observed between the groups thus suggesting a greater resistance to stress in casein groups than in soya groups.