Food Restriction Schedule Research Articles

Behavioral, Hormonal, and Serotonergic Responses to Different Restricted Feeding Schedules in Rats.

To determine the effect of long-term restricted feeding schedules on behavior, serotonergic responses, and neuro-endocrine functions, metabolism of serotonin (5-HT) in the striatum, expression of serotonin-1A (5-HT1A) auto-receptor in the raphe nuclei and circulating levels of leptin and corticosterone were determined in female Wistar rats kept on excessive food restriction schedule. Due to a role of dietary deficiency of tryptophan (Trp) in influencing serotonergic neurotransmission, circulating levels of Trp were also determined. Estimations were done in 2 different restricted feeding models: time-restricted feeding (TRF) and diet restricted (DR). TRF animals were given access to food ad libitum only for 2 hours/day. The DR animals were given a small calculated amount of food each day. We found that chronic food restriction for 5 weeks cause a significant decrease in the body weight and produced hyperactivity in both, TRF and DR animals. Levels of Trp were declined in circulation and in the striatum. Similarly, the levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were decreased in the striatum. Also, the expression of 5-HT1A auto-receptor was declined in the raphe nuclei. These changes in 5-HT metabolism and 5-HT1A auto-receptor expression were more profound in DR animals as compare to TRF animals. Similarly, hypoleptinemia and increased corticosterone found in both models was higher in DR animals. Effect of dietary deficiency of Trp in the modulation of striatal 5-HT metabolism and its consequences on circulating leptin and corticosterone are discussed.

Effects of ad libitum feeding and prefeeding on operant responding in sign- and goal-tracking rats

Sign-tracking and goal-tracking are behavioral tendencies in which Pavlovian conditioned responses are directed either toward the cue for an unconditioned stimulus (sign-tracking) or toward the location of an unconditioned stimulus delivery (goal-tracking). The current study examined operant response rates in sign- (n = 7) and goal-tracking (n = 11) Wistar rats under a restricted feeding schedule, ad libitum access to food, and reinforcer devaluation by prefeeding either the same or a different flavored pellet reinforcer. Only goal-tracking subjects significantly decreased their response rates after reinforcer devaluation by prefeeding, and only when the flavor used in prefeeding matched the reinforcer flavor. Both groups of subjects decreased responding under ad libitum food access compared to a 16-h food restriction schedule, but this effect size was larger in goal-tracking rats. These results extend recent findings that sign-trackers are more likely than goal-trackers to continue conditioned responding after unconditioned stimulus devaluation during operant conditioning.

Moderate intensity swimming training on bone mineral density preservation under food restriction in female rats

Abstract Aim: To investigate the effect of moderate-intensity swimming training on bone mineral density under a 20% food restriction (FR) schedule for 12 weeks in female rats. Methods: Forty female Wistar rats were distributed into four groups: control (CG), exercised (EG), food restriction (FRG), and food restriction/exercised (FREG). At 95 days, the animals were subjected to aquatic adaptation and then performed the critical load test to individually determine the critical load intensity (CLi, % of body mass). Exercised groups swam 5 days a week, 30 minutes daily with weekly adjustment of the load equivalent to 80% of the CLi. The FR schedule was 20% in relation to CG and started concomitantly with physical training (PT). After 12 weeks, visceral fat weight was recorded and the femur was collected for biophysical and biomechanical analysis. Results: FR and exercise training promoted visceral fat reduction (p<0.01). FR reduced bone mineral density (p<0.01), while exercise training prevented such reduction. On the other hand, FR and exercise training did not promote significant changes in biomechanical parameters of the femur. Conclusion: Exercise training at moderate intensity was efficient in preserving bone mineral density despite long term of FR at 20%.

Melanocortin-3 receptors are involved in adaptation to restricted feeding.

The central nervous melanocortin system forms a neural network that maintains energy homeostasis. Actions involving neural melanocortin-3 receptors (MC3Rs) regulate the expression rhythms in ingestive behaviors and metabolism anticipating nutrient intake. Here, we characterized the response of Mc3r knockout (Mc3r−/−) and wild type (WT) mice to a restricted feeding (RF) schedule where food access was limited to a 4-h period mid light cycle using a mechanical barrier. Mc3r−/− mice adapted poorly to the food restriction schedule. Anticipatory activity and the initial bout of intense feeding activity associated with granting food access were attenuated in Mc3r−/− mice, resulting in increased weight loss relative to controls. To investigate whether activity in specific hypothalamic nuclei contribute to the Mc3r−/− phenotype observed, we assessed hypothalamic FOS-immunoreactivity (FOS-IR) associated with food restriction. Food access markedly increased FOS-IR in the dorsomedial hypothalamus (DMH), but not in the suprachiasmatic or ventromedial hypothalamic nuclei (SCN and VMN, respectively) compared to ad libitum fed mice. Mc3r−/− mice displayed a significant reduction in FOS-IR in the DMH during feeding. Analysis of MC3R signaling in vitro indicated dose-dependent stimulation of the extracellular signal-regulated kinase (ERK) pathway by the MC3R agonist d-Trp(8)-γMSH. Treatment of WT mice with d-Trp(8)-γMSH administered intracerebroventricularly increased the number of pERK neurons 1.7-fold in the DMH. These observations provide further support for the involvement of the MC3Rs in regulating adaptation to food restriction. Moreover, MC3Rs may modulate the activity of neurons in the DMH, a region previously linked to the expression of the anticipatory response to RF.

Photic and Nonphotic Seasonal Cues Differentially Engage Hypothalamic Kisspeptin and RFamide‐Related Peptide mRNA Expression in Siberian Hamsters

Seasonally breeding animals use a combination of photic (i.e. day length) and nonphotic (e.g. food availability, temperature) cues to regulate their reproduction. How these environmental cues are integrated is not understood. To assess the potential role of two candidate neuropeptides, kisspeptin and RFamide-related peptide-3 (RFRP), we monitored regional changes in their gene expression in a seasonally breeding mammal exposed to moderate changes in photoperiod and food availability. Adult male Siberian hamsters (Phodopus sungorus) were housed under a long (16 h light/day; 16 L) or intermediate (13.5 L) photoperiod and fed ad lib. or a progressive food restriction schedule (FR; reduced to 80% of ad lib.) for 11 weeks. Gonadal regression occurred only in FR hamsters housed under 13.5 L. Immunohistochemistry was used to identify diencephalic populations of kisspeptin- and RFRP-immunoreactive cells, and quantitative PCR was used to measure gene expression in adjacent coronal brain sections. Photoperiod, but not food availability, altered RFRP mRNA expression in the dorsomedial sections, whereas food availability but not photoperiod altered Kiss1 expression in the arcuate sections; intermediate photoperiods elevated RFRP expression, and food restriction suppressed Kiss1 expression. Regional- and neuropeptide-specific activity of RFamides may provide a mechanism for integration of multi-modal environmental information in the seasonal control of reproduction.

Patterns of fos activation in rat raphe nuclei during feeding behavior

To analyze the differential recruitment of the raphe nuclei during different phases of feeding behavior, rats were subjected to a food restriction schedule (food for 2 h/day, during 15 days). The animals were submitted to different feeding conditions, constituting the experimental groups: search for food (MFS), food ingestion (MFI), satiety (MFSa) and food restriction control (MFC). A baseline condition (BC) group was included as further control. The MFI and MFC groups, which presented greater autonomic and somatic activation, had more FOS-immunoreactive (FOS-IR) neurons. The MFI group presented more labeled cells in the linear (LRN) and dorsal (DRN) nuclei; the MFC group showed more labeling in the median (MRN), pontine (PRN), magnus (NRM) and obscurus (NRO) nuclei; and the MFSa group had more labeled cells in the pallidus (NRP). The BC exhibited the lowest number of reactive cells. The PRN presented the highest percentage of activation in the raphe while the DRN the lowest. Additional experiments revealed few double-labeled (FOS-IR + 5-HT-IR) cells within the raphe nuclei in the MFI group, suggesting little serotonergic activation in the raphe during food ingestion. These findings suggest a differential recruitment of raphe nuclei during various phases of feeding behavior. Such findings may reflect changes in behavioral state (e.g., food-induced arousal versus sleep) that lead to greater motor activation, and consequently increased FOS expression. While these data are consistent with the idea that the raphe system acts as gain setter for autonomic and somatic activities, the functional complexity of the raphe is not completely understood.

Augmented Acquisition of Cocaine Self-Administration and Altered Brain Glucose Metabolism in Adult Female but not Male Rats Exposed to a Cannabinoid Agonist during Adolescence

Marijuana consumption during adolescence has been proposed to be a stepping-stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self-administration (1 mg/kg), food-reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food-restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [(18)F]-fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP-treated rats showed a higher rate of cocaine self-administration as compared to vehicle-treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food-reinforced operant task, pointing to the cocaine-specific nature of the effect seen in self-administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP-treated females when compared to their vehicle-treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo-entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self-administration, in a sex-specific fashion. This increased susceptibility could be related to the changes in brain metabolic activity induced by cannabinoids during adolescence.

The effects of chronic food restriction on hypothalamic–pituitary–adrenal activity depend on morning versus evening availability of food

Partial food restriction (FR) protocols have been used not only to study behavioral and physiological consequences of decrease food intake, but as a necessary treatment of the animals in some operant learning tasks. It is well-established in rodents that restricting food availability to a few hours in the morning causes an alteration of the daily rhythm of corticosterone, thus making it difficult to evaluate whether or not such treatments are stressful. In the present experiment adult male Sprague–Dawley rats were subjected to two different FR schedules: food availability after 1100 h (LFR) or after 1900 h (DFR). After 14 days, animals from both groups, together with corresponding controls, were killed under resting conditions, either in the morning or in the evening, just before daily access to food in FR rats. Both FR schedules reduced body weight gain to the same extent, but their impact on the hypothalamic–pituitary–adrenal (HPA) axis was different: DFR increased relative, but not absolute, adrenal weight and morning and evening levels of corticosterone, whereas LFR increased both absolute and relative adrenal weights and increased morning corticosterone levels to a greater extent than DFR rats. Neither serum ACTH nor corticotropin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus were altered by DFR or LFR protocols, suggesting that factors other than CRF and ACTH are involved in the control of adrenocortical secretion under FR. It appears that LFR caused more alterations in the HPA axis than DFR and, therefore, the latter FR schedule should be used in those protocols necessarily involving partial FR.

Entrainment of Aged, Dysrhythmic Rats to a Restricted Feeding Schedule

Aged rats often display abnormal circadian activity rhythms; the rhythm amplitude is low and entrainment to light-dark cycles is irregular. The activity rhythm of young rats can be entrained by both light and nonphotic cues, specifically food availability. In young rats, entrainment to restricted feeding cycles does not depend on intact suprachiasmatic nuclei, the presumed anatomical location of the light-entrainable oscillator. In this study, aged rats that displayed disrupted entrainment to light were assessed for their ability to entrain to restricted feeding schedules. Aged rats, young controls, and young suprachiasmatic nuclei-lesioned (SCN) rats were placed on a food restriction schedule (FR) for 14 days. Food was available for 2 h during the light phase of a 12-h light-dark cycle. Despite the absence of entrainment to light/dark cycles, both SCN-lesioned and aged groups showed entrainment to FR, with clear bouts of anticipatory activity during a period of complete food deprivation following 2 weeks of FR. The results suggest that the dysrhythmia of aged rats is a result of natural deterioration of a central circadian light-entrainable pacemaker, but that a secondary oscillator entrainable to food cycles is spared.

Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats.

Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.

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.

The effects of naloxone on body rotation-induced analgesia and anorexia in male mice

The effects of body rotation in a horizontal plane and the opiate antagonist, naloxone, on the nociceptive responses and the feeding behavior of male mice were examined. In the first experiment the mice were rotated (70 rpm, schedule of 15 sec on; 5 sec off) for 60 minutes or exposed to sham rotation for the same duration. Midway through the rotation or sham procedure the mice were either injected with naloxone (1 mg/kg) or isotonic saline. At the end of the 60-minute treatment period the animals were placed on a warm surface (47.5°C) and their latency to show a foot-licking response was measured. The rotation procedure produced a significant ( p<0.01) increase in response latency in the saline-injected mice and the naloxone injections blocked this analgesic effect. This finding provides evidence for opioid involvement in the rotation-induced analgesia. In experiment 2 mice on a food restriction schedule were rotated (70 rpm, 15 sec on; 5 sec off) or sham exposed for 60 minutes. Midway through this treatment period the mice were either injected with naloxone (1 mg/kg) or isotonic saline. Following the treatment period the mice were given access to food for 2 hours. The rotation procedure produced a significant ( p<0.01) reduction in feeding (anorexia) in the first 30 minutes of food access for the saline-injected mice. Injections of naloxone significantly ( p<0.05) enhanced the rotation-induced anorexia. These experiments demonstrate that rotation-induced analgesia in mice is blocked by the opiate antagonist, naloxone, whereas rotation-induced anorexia is not. Further, naloxone was found to enhance rotation-induced anorexia, possibly by intensifying rotation induced motion sickness in the mice.

Effects of food restriction during concurrent lactation and pregnancy in the rat

The ability of rat dams to cope with food restriction as well as a concurrent lactation and pregnancy was examined by varying the duration, time of onset and severity of the food restriction schedule. Groups of females impregnated in the postpartum estrus and nursing 8 pups were either allowed to feed ad lib, given 60% of an ad lib ration from days 1–7, 1–14, 8–14 or 15–21 postpartum or 40% of an ad lib ration from days 1–7. Food restriction regimens that extended through the estimated time of implantation for females nursing 8 pups (days 1–14 and 8–14) resulted in a prolongation of pregnancy. Food restriction in the first week postpartum did not result in a prolongation of pregnancy and did not affect the number of females carrying the pregnancy to term. Dams food restricted in the third week postpartum had pregnancies of the same length as ad lib females but a smaller proportion of this group gave birth to a second litter.

Metabolic changes of twenty weeks food-restriction schedule in rats

In previous studies several metabolic and hormonal adaptations were detected as a consequence of food restriction schedule (single daily meal offered during two hours from 7:30 to 9:30 a.m.) imposed for four weeks. During this period, the most prominent metabolic adaptations were: (1) high alimentary efficiency, (2) delayed gastric emptying, (3) high hepatic glycogen concentration during the intermeal periods, (4) glycemic maintenance during 22 hours of intermedal period as were low mobilization of free fatty acids. In the present work these metabolic adaptations were studied for twenty weeks. The results obtained show that the metabolic and hormonal pattern, defined during four weeks of training to such alimentary scheme, was maintained even after the 20th week. Moreover, it was clear that neither did the body weight increase rapidly nor did it reach that of free-fed rats, after adaptation phase, as reported by other authors.

Effects of age and feeding regimen on protein and carbohydrate self-selection

The effects of age and restricted daily feeding on dietary self-selection were examined as these variables are already known to affect feeding behaviour, protein requirements and central neurotransmitter metabolism. Absolute levels of energy and protein intake, or the ratio of protein to total energy consumed, did not differ between adult and weanling free-feeding rats. A daily 16-h food restriction schedule increased energy intake and body weight gain in adult rats but decreased these parameters in weanlings. However, food restriction significantly decreased protein intake and the ratio of protein to total energy consumed in both adult and weanling rats. These results show that these variables can interact to alter dietary self-selection and have implications for work using drugs under deprived or free-feeding conditions.