Modifications pharmacologiques du comportement alimentaire: prise de nourriture et rumination chez le mouton

Summary The effects of 10 psychotropic drugs on food intake and rumination were studied in six sheep under carefully controlled conditions.Criteria used to analyse food intake and rumination included total times spent ruminating and food intake during 3 months and 3 days before and after each injection of the drug.Imipramine, ephedrine, cafeine, methylphenidate, tranylcypromine, nialamide in appropriate doses all reduced both food intake and rumination.Mescaline, apomorphine, morphine and amphetamine induced some compulsive chewing and feeding.Digitaline and lanatoside C caused the animals to reduce their time spent ruminating.Reserpine reduced feed consumption without affecting rumination. The feed consumption and chiefly rumination are increased by chlorpromazine and, to some extent, by pentobarbital.     

Cannabinol and cannabidiol exert opposing effects on rat feeding patterns

Rationale

Increased food consumption following ?⁹-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented. However, possible non-?⁹-tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors.

Methods

Adult male rats were treated (p.o.) with cannabigerol, cannabidiol, cannabinol or cannabinol plus the CB₁R antagonist, SR141716A. Prior to treatment, rats were satiated and food intake recorded following drug administration. Data were analyzed for hourly intake and meal microstructure.

Results

Cannabinol induced a CB₁R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior.

Conclusion

This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ?⁹-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic. Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.     

Metabolic and behavioral effects of olanzapine and fluoxetine on the model organism Caenorhabditis elegans

The use of many psychotropic drugs (PDs) is associated with increased caloric intake, significant weight gain, and metabolic disorders. The nematode Caenorhabditis elegans (C. elegans) has been used to study the effects of PDs on food intake. However, little is known about PDs effects on the body fat of C. elegans. In C. elegans, feeding behavior and fat metabolism are regulated through independent mechanisms. This study aims to evaluate the body fat and food intake of C. elegans in response to treatment olanzapine and fluoxetine. Here we report that, with careful consideration to the dosage used, administration of fluoxetine and olanzapine increases body fat and food intake in C. elegans.     

Action of excess calcium ions in the brain on motivated feeding in the rat: attenuation by pharmacological antagonists

The intraventricular infusion of 5 μl of physiological solution in which the concentration of calcium ions was adjusted from 1.26 mM to 151.2 mM caused spontaneous feeding and drinking in the satiated rat. The ingestive response was observed both when pellets and water freely available, in which case food consumption exhibited a dose-response relationship increasing with the millimolarity of calcium in the infusate, and when operant responses at FR 2 or FR 10 were required for food reward. The rate of bar pressing by an animal at these two schedules of reinforcement did not differ from that observed when the same animal was deprived of food and water for 23 hr. The alpha-adrenergic antagonist, phentolamine (16 μg, 32 μg), did not appreciably attenuate Ca²⁺-induced feeding during either ad lib or motivated conditions, though these doses drastically reduced food intake induced by the intraventricular infusion of 10 μg norepinephrine HCl. The pre-infusion of a number of additional blocking agents had variable yet consistent effects upon Ca²⁺-induced feeding; hexamethonium (8 μg, 25 μg), propranolol (6 μg, 28 μg) and methysergide (8 μg) each caused a statistically significant enhancement in the magnitude of the Ca²⁺ response while atropine (6 μg, 15 μg) significantly attenuated feeding after Ca²⁺. This suggests an interaction between a number of pharmacologically distinct fiber pathways that may mediate the Ca²⁺ feeding response. The modulation of feeding by Ca²⁺ ions supports an ionic theory for the regulation of body weight in the rat, in which neurons that are involved in ingestive responses and which pass through the hypothalamus and other structures along the ventricular lumen are selectively sensitive to the concentration of calcium in the extracellular fluid.     

Safety assessment of transgenic canola RF3 with bar and barstar gene on Sprague-Dawley (SD) rats by 90-day feeding test

Canola is one of the most important plant oilseed crops. To avoid the threat of herbicides, the RF3 line with bar gene and barstar gene was developed, which can act as glufosinate resistance resources and restore fertility in hybrid lines. To assess the food safety of transgenic canola RF3, 2.5%, 5% and 10% GM canola RF3 and its non-GM isogenic line Drakkar were formulated into diet to feed Spragure-Dawley (SD) rats for 90 days. The effects on the general growth and toxicological parameters, as well as gut microbiota of rats, were evaluated. Several significant differences on body weight, feed consumption, relative organ weight, hematology and serum biochemistry were observed among rats in the 90-day feeding test. However, these statistical differences were randomly observed among different groups and were not dose-related, which were not considered to be biologically significant. Furthermore, the results of bacterial 16S rRNA sequencing of fecal samples showed that the diets containing GM canola did not disturb the balance of gut microbiota. In conclusion, the canola RF3 is considered as safe and wholesome as the non-GM canola based on this 90-day feeding test and gut microbiota analysis.     

Feeding parameters with two food textures after chlordiazepoxide administration,alone or in combination with d-amphetamine or fenfluramine

Chlordiazepoxide (5.0, 10.0 mg/kg) reduced the rate of eating and extended the duration of feeding in a 10 min feeding test. It also reduced the latency to feed. Both fenfluramine (1.0 mg/kg) and d-amphetamine (0.25 mg/kg) acted to reduce food intake, but by differing mechanisms. Fenfluramine reduced eating rate without affecting eating duration, whilst d-amphetamine reduced eating duration without reducing eating rate. The effects of chlordiazepoxide on feeding parameters were generally additive with those of either d-amphetamine or fenfluramine, whenever chlordiazepoxide was given in combination with one of the anorectic drugs. Food texture affected feeding behaviour; rats ate standard diet in pellet form faster than powdered food, although they spent longer eating the powdered food. Textural differences did not significantly interact with the changes in feeding responses induced by the 3 drugs, except that latency to eat after either d-amphetamine or fenfluramine injection, when pellets were available, was significantly prolonged. Characterising drug effects on feeding in terms of a 2-dimensional matrix of eating rate and duration is recommended, rather than relying solely on amount of food consumption as the measure of drug effects.     

Chlorpromazine specifically prevents the wheel-induced feeding suppression in rats

In rats, limited daytime wheel access suppresses feeding over the subsequent night [Lattanzio SB, Eikelboom R. Wheel access duration in rats: I. effects on feeding and running. Behav Neurosci 2003; 117:496–504.]. This phenomenon is known as the wheel-induced feeding suppression (WIFS). The classic antipsychotic, chlorpromazine, can minimize the severity of the related activity anorexia procedure, but is thought to act through a suppression of running [Routtenberg A. “Self-starvation” of rats living in activity wheels: adaptation effects. J Comp Physiol Psychol 1968; 66:234–8.]. We tested the effects of chlorpromazine (2 mg/kg IP) on the acute WIFS in 40 adult male rats by administering the drug before or after 3 h of daytime wheel access and measuring food consumption over the subsequent 24 h. Control groups received saline injections or were exposed to locked wheels. While chlorpromazine did not attenuate feeding or change wheel running alone, it blocked their interaction, the acute WIFS. This procedure might be useful in screening drugs for anorexia nervosa where exercise is often elevated and feeding is suppressed.     

Characterization of the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Treatment of male rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a dose-dependent decrease in body weight, feed intake, resting and total oxygen consumption, and spontaneous motor activity. In animals treated with a nonlethal dose (5 or 15 μg/kg), feed intake and oxygen consumption recover within 3 weeks post-treatment to levels appropriate for the reduced weight of the animals. Rats treated with a lethal dose (50 μg/kg) lose weight continuously after treatment and typically die at a body weight approximately half that of age-matched, control rats. The similar dose and time dependencies for reduction of feed intake and weight suggest that hypophagia is the major factor responsible for weight loss in TCDD-treated rats. To determine if this hypophagia is a primary or secondry effect of TCDD treatment, rats whose body weights were reduced by food restriction prior to treatment (25 μg/kg) were studied. When allowed to feed ad libitum immediately after treatment, these animals exhibited relative hyperphagia and weight gain demonstrating that TCDD did not impair their capacity to feed. This finding suggests that the primary effect of TCDD is not on a system that controls feed intake, but rather on one that regulates body weight. It is proposed, as a heuristic model of the wasting syndrome, that TCDD treatment lowers a “set point” for regulated body weight in the rat in a dose-dependent fashion and that hypophagia serves, as a secondary response, to reduce the animal's weight to the lower regulation level determined by the dose administered.     

Acute and chronic effects of δ9-tetrahydrocannabinol on food intake by rats

The effects of intraperitoneally injected ⁹-tetrahydrocannabinol (THC) were compared with d-amphetamine sulfate (d-AMP) on food intake in rats which were given access to food for 6 hrs each day. Food intake was markedly reduced in a dose-related fashion by THC (2.5 and 5.0 mg/kg) in the first 2 hrs after drug administration. This anorexic effect persisted for the next 4 hrs and even on the next day. The anorexic potency of d-AMP (1.25 and 2.5 mg/kg) was approximately twice that of THC in the initial 2-hrs interval after a single dose, but during the next 4 hrs and on the next day there was a compensatory increase in food consumption. Daily administration of THC (2.5 mg/kg) for 9 days greatly decreased food intake and body weight gain of animals which were injected immediately before feeding, but had little effect on animals injected 16 hrs before feeding.     

Lipid-soluble green tea extract: Genotoxicity and subchronic toxicity studies

To assess the potential safety of lipid soluble green tea extract, also referred to as lipid soluble tea polyphenols (LSTP), a series of genotoxicity tests were conducted, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality test. The toxicity of LSTP was evaluated in 90- and 30-day feeding studies. LSTP did not show mutagenic activity in the Ames test and no genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). In the 90-day feeding study, LSTP was given in the diet at levels providing 0, 0.125, 0.25, or 0.50 g/kg bw/day. No significant effects were noted on body weight, food consumption, hematology, clinical chemistry, organ weights, and histopathological examination. The no-observed-adverse-effect level (NOAEL) was therefore considered to be 0.50 g/kg bw/day, the highest dose tested. Likewise, dosing of SD rats by gavage for 30 days also showed no adverse effects of growth, hematology, clinical chemistry, organ weights, or histopathology at doses of 0.58, 1.17, and 2.33 g/kg bw/day. The NOAEL in the 30-day study was considered to be the highest dose tested. These data provide evidence to support the safe use of LSTP in food.     

Beeinflussung des Nahrungs- und Trinkverhaltens von Ratten durch getrenntes Futter- und Wasserangebot sowie durch Pharmaka

Summary Food and water consumption of albino rats was limited to three hours daily. From the three groups tested the first group received both food and water simultaneously, the second group was given food first and water afterwards and the third group water first and food afterwards. Rats of the first and second group consumed reasonable amounts of food and water and managed to maintain body weight. The rats of the third group however, (water first, food second) consumed less water and food, lost considerable weight and died within two to four weeks. We do not know why this change in the order of feeding seems to be so important.In the above mentioned groups the action of certain drugs upon food and water intake was tested. In order to measure the effect on water and food intake separatly the drugs were administered after dry food consumption in the first experiment and after water intake in the second experiment. By this method we eliminated the effect of food on water intake and water on food intake. d-Amphetamin, Preludin (2-phenyl-3-methyltetrahydro-1,4-oxazin · HCl), Caffeine sodium salicylate and Chlorpromazine reduced food and water intake independently whereas Sodium Phenobarbital increased food and water consumption independently. Moreover it is pointed out that testing appetite functions can help a lot in further characterization of centrally acting drugs.

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The in vivo effect of Cordyceps sinensis mycelium on plasma corticosterone level in male mouse

Cordyceps sinensis (CS), an Ascomycetes fungus parasitic to Lepidoptera larvae, has been traditionally used as nutritious food for the enhancement in immuno-modulation in Chinese society for a long time. Previous report has demonstrated the CS water extract stimulates in vitro corticosterone production in rat primary adrenal cells. In the present studies, we determined the in vivo effects of CS and its fractions on plasma corticosterone production in mouse. Different concentrations of CS and CS fractions dissolved in water (0.02 and 0.2 mg/g body weight) were fed to immature and mature mice from 1, 3 or 7 d. The plasma levels of corticosterone were determined by radioimmunoassay (RIA), and the weight of adrenal gland and body weight were also evaluated. Results illustrated that plasma corticosterone levels were significantly induced by F2 at 0.02 mg/g body weight with 7 d feeding in immature mice, and by CS at 0.02 mg/g body weight with 3 d feeding and F3 at 0.02 mg/g body weight for 7 d feeding in mature mice, respectively (p < 0.05). There were no differences of adrenal gland weight except there was significant stimulation by CS at 0.2 mg/g body weight with 3 d feeding in mature mice (p < 0.05) and there were significant inhibitions by both dosages of F3 for 3 d feeding in immature mice and F2 for 7 d feeding in mature mice (p < 0.05), respectively. Concerning body weight, the stimulatory effects were observed with CS feeding at 0.2 mg/g body weight for 7 d and F3 feeding at 0.02 mg/g body weight for 3 and 7 d in mature mice. Whereas, the inhibitory effect were observed in F2 feeding at 0.2 mg/g body weight for 7 d in immature mice and at both dosages for 7 d in mature mice, respectively. Taken together, these studies illustrate that CS and its fractions stimulated mouse in vivo corticosterone production. However, CS and its fractions didn't have constant stimulatory or inhibitory effects on the weights of body and adrenal glands.     

The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain

The effect of a variety of psychotropic drugs, given to rats repeatedly over 16 days, on the number of beta-adrenergic receptor binding sites in cerebral cortex was measured. Labelled dihydroalprenolol, [³H]-DHA, was used to measure beta-adrenergic binding sites. Both tricyclic antidepressants (amitriptyline, chlorimipramine, desmethylimipramine and nortriptyline) and monoamine oxidase inhibitors (nialamide and tranylcypromine) lowered [³H]-DHA binding significantly. Repeated treatment of rats with the antidepressant. iprindole. produced the same effect as did treatment with bupropion. However, the experimental antidepressant mianserin did not reduce [³H]-DHA binding nor did 11 other psychoactive compounds including chlorpromazine, diazepam, l-DOPA, tripelennamine and cocaine. The reduction in [³H]-DHA binding produced by nialamide or iprindole treatment was due to a reduction in the maximum number of beta-adrenergic receptor binding sites. Drug treatment-induced lowering of [³H]-DHA binding sites in cerebral cortex appears to have utility as a pre-clinical test for antidepressant drugs.     

Chlorpromazine specifically prevents the wheel-induced feeding suppression in rats

In rats, limited daytime wheel access suppresses feeding over the subsequent night [Lattanzio SB, Eikelboom R. Wheel access duration in rats: I. effects on feeding and running. Behav Neurosci 2003; 117:496–504.]. This phenomenon is known as the wheel-induced feeding suppression (WIFS). The classic antipsychotic, chlorpromazine, can minimize the severity of the related activity anorexia procedure, but is thought to act through a suppression of running [Routtenberg A. “Self-starvation” of rats living in activity wheels: adaptation effects. J Comp Physiol Psychol 1968; 66:234–8.]. We tested the effects of chlorpromazine (2 mg/kg IP) on the acute WIFS in 40 adult male rats by administering the drug before or after 3 h of daytime wheel access and measuring food consumption over the subsequent 24 h. Control groups received saline injections or were exposed to locked wheels. While chlorpromazine did not attenuate feeding or change wheel running alone, it blocked their interaction, the acute WIFS. This procedure might be useful in screening drugs for anorexia nervosa where exercise is often elevated and feeding is suppressed.     

Suitability test of various food mixtures for breeding and rearing of beagle dogs. 2nd Communication: Methods and results of feeding experiments of the Mannheim team (author's transl)]

A comparison of 3 commercially available dog foods (Ssniff C, Altromin H, Altromin HW) with 2 newly formulated dog food mixtures was carried out with regard to breeding, rearing and maintenance of Beagle dogs. No significant differences were found between the individual feeding groups with regard to the fertility and breeding ability of the bitches. All the foods supplied the requirements for energy, nutrients and feed additives in the rearing and maintenance of the dogs. The parameters used for the assessment, such as body weight, daily gain, daily food consumption and feed efficiency, were satisfactory for all food groups and were partially reproduceable. If the consumption of food, energy and nutrients per kg body weight are calculated and are related to the rearing results obtained then inconsistencies occur which can only be explained by differences in digestibility of the individual food components, and these underline the need for digestibility tests in dogs. The 2 newly formulated foods compared favourably with the other food stuffs and fulfilled the requirements for better standardised food mixtures. Further experiments will investigate the effects on the morphological, haematological and clinico-chemical characteristics. A comparison of different age groups confirmed the data in the literature which indicates that younger animals have a higher requirement for energy and nutrients per kg body weight than older animals. Results that have not yet been explained are the findings that the consumption of food, and thus of energy and nutrients, per kg body weight in younger male animals is lower than that of the female animals of the same age to a highly significant degree.     

Safety assessment of powdered Cistanche deserticola Y. C. Ma by a 90-day feeding test in Sprague-Dawley rats

Cistanche deserticola (C. deserticola), a holoparasitic plant widely distributed in arid or semi-arid areas in Eurasia and North Africa, has been used as an important tonic in traditional Eastern medicine for centuries. However, little information on the systemic toxicity and safety evaluation of it is available. The purpose of this study was to investigate the potential toxicity of powdered C. deserticola as a novel food ingredient by use of a subchronic toxicity study in Sprague-Dawley (SD) rats. A total of 80 male and female rats were fed with diets containing 8, 4, 2 and 0% (control) powdered C. deserticola for 90 days. A toxicological assessment was performed including mortality, body and organ weight, food consumption, blood biochemistry, hematology, gross necropsy and histopathological examinations. There were no signs of toxicity and treatment-related changes in rats treated with powdered C. deserticola. The no-observed-adverse-effect level (NOAEL) of powdered C. deserticola was 7.8?g?kg^?1 body weight for males and 8.0?g?kg^?1 body weight for females of rats under the experimental conditions of this study.     

Hepatoprotective Activity of Polyherbal Formulation (Normeta®) in Oxidative Stress Induced by Alcohol,Polyunsaturated Fatty Acids and Iron in Rats

Abstract: In recent years, oxidative stress has been implicated in the pathophysiology of a large number of diseases or disorders which are initiated and/or exacerbated by pro‐oxidants such as various drugs including alcohol and food additives. The present study was carried out to evaluate the effects of oral treatment with polyherbal formulation Normeta^® (2 ml and 4 ml/kg) on hepatic damage induced by alcohol 10–30% (blood alcohol was maintained at levels between 150 and 350 mg/dl), thermally oxidized oil (polyunsaturated fatty acids) (15% of diet) and carbonyl iron (1.5–2% of diet) for 30 days in rats. In vitro studies with 1, 1‐Diphenyl, 2‐Picrylhydrazyl (DPPH), Nitric oxide and Ferric chloride (Fe⁺³ ions) showed that Normeta^® possesses antioxidant and metal chelating activity. Alcohol, polyunsaturated fatty acids and iron feeding produced an increase in serum levels of iron, serum glutamate pyruvate transaminase and decrease in serum proteins. It was also associated with elevated lipid peroxidation (thiobarbituric acid reactive substances) and disruption of antioxidant defence mechanism in liver, decreased body weight and increased liver to body weight ratio. Oral administration of Normeta^® along with alcohol, polyunsaturated fatty acids and iron decreased the serum iron, serum glutamate pyruvate transaminase levels and increased serum protein levels. The levels of liver thiobarbituric acid reactive substances were decreased and the activities of antioxidant enzymes superoxide dismutase and catalase were increased. Improvement in body weight and liver to body weight ratio was also observed. The effects of Normeta^® on physico‐metabolic parameters were comparable with silymarin. This indicates that Normeta^® has favourable effect in bringing down the severity of hepatotoxicity.     

Alteration of the disruptive effect of fenfluramine on food consumption in the rat by repeated post-session administration of d-amphetamine

The purpose of this study was to determine whether repeated treatment (15 days) with d-amphetamine (AMP) or fenfluramine (FEN), administered after a daily 3 h feeding session (e. g. post-session), would result in tolerance or crosstolerance to the decrement in food consumption induced by treatment with either drug before feeding (e. g. pre-session). Groups of male rats were treated IP with 0.5 ml saline, 1.0, 2.0, or 4.0 mg/kg AMP, or 2.5, 5.0, or 10.0 mg/kg FEN prior to a 3 h feeding session. For the next 15 sessions, the respective groups were treated post-session with saline (0.5 ml), AMP (4.0 mg/kg), or FEN (10 mg/kg). Following the 15 day postsession phase, each group again received this pre-session treatment. The initial pre-session treatment with all dosages of these two drugs produced a significant decrease in food consumption. Tolerance to the food intake suppressant effect of FEN, but not AMP, resulted from repeated post-session treatment with the same agent. Repeated post-session treatment with AMP resulted in a significant decrement in the suppressant activity of FEN on food intake, whereas the corresponding post-session treatments with FEN did not alter the pre-session effects of AMP, except for an enhancement seen with higher AMP doses.     

Dietary toxicity of soluble and insoluble molybdenum to northern bobwhite quail (<Emphasis Type="Italic">Colinus virginianus</Emphasis>)

Limited data are available on the effects of molybdenum (Mo) on avian wildlife, which impairs evaluation of ecological exposure and risk. While Mo is an essential trace nutrient in birds, little is known of its toxicity to birds exposed to molybdenum disulfide (MoS₂), the predominant form found in molybdenite ore. The chemical form and bioavailability of Mo is important in determining its toxicity. Avian toxicity tests typically involve a soluble form of Mo, such as sodium molybdate dihydrate (SMD, Na₂MoO₄·2H₂O); however MoS₂ is generally insoluble, with low bioaccessibility under most environmental conditions. The current study monitored survival and general health (body weight and food consumption) of 9-day old northern bobwhite exposed to soluble Mo (SMD) and ore-related Mo (MoS₂) in their diet for 30 days. Toxicity and bioavailability (e.g. tissue distribution) of the two Mo forms were compared. Histopathology evaluations and serum, kidney, liver, and bone tissue sample analyses were conducted. Copper, a nutrient integrally associated with Mo toxicity, was also measured in the diet and tissue. No treatment-related mortality occurred and no treatment-related lesions were recorded for either Mo form. Tissue analyses detected increased Mo concentrations in serum, kidney, liver, and bone tissues following exposure to SMD, with decreasing concentrations following a post-exposure period. For the soluble form, a No-Observed-Adverse-Effect Concentration (NOAEC) of 1200 mg Mo as SMD/kg feed (134 mg SMD/kg body weight/day) was identified based on body weight and food consumption. No adverse effects were observed in birds exposed to MoS₂ at the maximum dose of 5000 mg MoS₂/kg feed (545 mg MoS₂/kg body weight/day). These results show that effects associated with MoS₂, the more environmentally prevalent and less bioavailable Mo form, are much less than those observed for SMD. These data should support more realistic representations of exposure and risks to avian receptors from environmental Mo.     

The impact of early undernutrition on voluntary food consumption in later life of rats.

Food consumption patterns were studied during ad-libitum feeding of rats undernourished for 21 or 60 days after birth. Rats undernourished for 21 days consumed less food than the controls on a whole animal basis. But the food intake was higher during the early part of ad-libitum feeding when expressed on a unit body weight or metabolic body weight basis, and subsequently became comparable to that of the controls. Male rats undernourished for 60 days showed either comparable (for the whole animal) or higher (in other terms) food consumption, whereas the female rats undernourished for 60 days consumed more food at the beginning of ad-libitum feeding but less food during the latter part, when compared to their respective controls. The results thus indicate that no single mechanism can completely explain the food intake of undernourished rats during nutritional rehabilitation.