Self-imposed food deprivation and wheel-running activity in field-trapped Norway rats as a function of environmental change,time in captivity and age at capture

The tendency of juvenile and adult field-trapped Norway rats (Rattus norvegicus) to exhibit self-induced food deprivation in response to changes in their living environment was studied after different periods of residency in the laboratory environment. Self-imposed food deprivation resulting from the forced occupation of a novel environment (activity wheels) was greater for those animals tested immediately upon capture and after 25 weeks in captivity than for rats in captivity for 4 weeks. The deprivation response of juveniles was less than for adults immediately following capture but after 25 weeks in captivity the responses of the two age groups were similar. Deprivation responses following reintroduction to the home cage environment diminished over time in captivity. Wheel-running by adults was greatest immediately following capture whereas juveniles continued to show relatively high levels of wheel-running at 4 weeks in captivity. The results are discussed in terms of habituation to the laboratory environment and time-dependent changes in response to novelty.     

Competitive dominance of wild and domestic Norway rats (Rattus norvegicus)

The objective was to determine differences in the relative dominance of wild and domestic Norway rats (Rattus norvegicus) when competing for food in inter-stock, round-robin pairings. Each day, after food-deprivation, wild and domestic rats were individually placed in a testing arena containing a slice of apple. On day 20 and every fourth day thereafter, eight wild-domestic pairs were allowed to compete for the apple. Domestic subjects spent more time eating than did wild rats and were more often dominant. Competition tended to wane over test days in response to defeat in earlier trials. The outcome of competition trials was not changed by increasing the extent of food deprivation together with continuous pairing. A reduction in social inhibitions accompanying the domestication process provides the best explanation for the enhanced competitive potential of the domestic rat.     

Food-deprivation-induced phase shifts in Sminthopsis macroura froggatti

Past research has shown that there is a circadian oscillator in laboratory rats that is entrained by restricted feeding schedules. However, in laboratory rats at least, the light-dark (LD) cycle is the dominant zeitgeber in the entrainment of wheel-running activity rhythms. Given that dasyurid marsupials are predominantly carnivorous, the episodic intake of food in the wild and the high nutritive content of that food suggest that food may be an important zeitgeber in these species. Twelve Sminthopsis macroura froggatti were presented with a daily meal at 0900 hr under an LD 12:12 cycle with lights-on at 0600 hr for 37 days. Activity in anticipation of the meal was observed in most animals. Following this, all animals were exposed to periods of 12-18 days ad lib. food interspersed with 3-day periods of deprivation--a technique used previously to demonstrate persistent meal-associated rhythms. The meal-associated activity rhythms previously observed in rats during the 3-day deprivation period were not seen, but the 3-day deprivation period produced large phase-shifts in the activity rhythms of several S.m. froggatti. It is concluded that meal feeding does not dominate the LD cycle in entraining dasyurid marsupials, but that the frequent observation of phase shifts suggests a different and, perhaps, stronger role for food intake in biological rhythmicity than has been observed previously in laboratory rats.     

Inhibition of voluntary activity by growth hormone

During food deprivation and subsequent refeeding there are alterations in growth hormone (GH) secretion and wheel-running activity such that wheel running increases when GH secretion decreases and vice versa. To investigate if there might be a causal relationship between GH secretion and wheel running, the effect of GH administration on wheel running was studied. Female Sprague-Dawley rats were placed singly in activity-wheel cages shortly after weaning. Beginning at 70–75 days of age the rats received 14 daily control injections of saline followed by 14 daily injections of GH and a further 14 days of control injections. Wheel-running activity was inhibited during the period of growth hormone injections. Possible implications of this result are discussed.     

Differential metabolic response to 48 h food deprivation at different periods of pregnancy in the rat

Since during pregnancy the mother switches from an anabolic to a catabolic condition, the present study was addressed to determine the effect of 48 h food deprivation on days 7, 14 and 20 of pregnancy in the rat as compared to age matched virgin controls. Body weight, free of conceptus, decreased with food deprivation more in pregnant than in virgin rats, with fetal weight (day 20) also diminishing with maternal starvation. The decline of plasma glucose with food deprivation was greatest in 20 day pregnant rats. Insulin was highest in fed 14 day pregnant rats, and declined with food deprivation in all the groups, the effect being not significant in 7-day pregnant rats. Food deprivation increased plasma glycerol only in virgin and 20 day pregnant rats. Plasma NEFA and 3-hydroxybutyrate increased with food deprivation in all groups, the effect being highest in 20 day pregnant rats. Food deprivation decreased plasma triacylglycerols in 14 day pregnant rats but increased in 20 day pregnant rats. In 20-day fetuses, plasma levels of glucose, NEFA and triacylglycerols were lower than in their mothers when fed, and food deprivation caused a further decline in plasma glucose, whereas both NEFA and 3-hydroxybutyrate increased. Liver triacylglycerols concentration did not differ among the groups when fed, whereas food deprivation caused an increase in all pregnant rats and fetuses, the effect being highest in 20-day pregnant rats. Lipoprotein lipase (LPL) activity in adipose tissue was lower in 20 day pregnant rats than in any of the other groups when fed, and it decreased in all the groups with food deprivation, whereas in liver it was very low in all groups when fed and increased with food deprivation only in 20 day pregnant rats. A significant increase in liver LPL was found with food deprivation in 20 day fetuses, reaching higher values than their mothers. Thus, the response to food deprivation varies with the time of pregnancy, being lowest at mid pregnancy and greatest at late pregnancy, and although fetuses respond in the same direction as their mothers, they show a specific response in liver LPL activity.     

Food-Entrained Feeding and Locomotor Circadian Rhythms in Rats Under Different Lighting Conditions

It has been suggested that two endogenous timekeeping systems, a light-entrainable pacemaker (LEP) and a food-entrainable pacemaker (FEP), control circadian rhythms. To understand the function and interaction between these two mechanisms better, we studied two behavioral circadian rhythmicities, feeding and locomotor activity, in rats exposed to two conflicting zeitgebers, food restriction and light-dark cycles. For this, the food approaches and wheel-running activity of rats kept under light-dark (LD) 12:12, constant darkness (DD), or constant light (LL) conditions and subjected to different scheduled feeding patterns were continuously recorded. To facilitate comparison of the results obtained under the different lighting conditions, the period of the feeding cycles was set in all three cases about Ih less than the light-entrained or free-running circadian rhythms. The results showed that, depending on the lighting conditions, some components of the feeding and wheel-running circadian rhythms could be entrained by food pulses, while others retained their free-running or light-entrained state. Under LD, food pulses had little influence on the light-entrained feeding and loco-motor rhythms. Under DD, relative coordination between free-running and food-associated rhythms may appear. In both cases, the feeding activity associated with the food pulses could be divided into a prominent phase-dependent peak of activity within the period of food availability and another afterward. Wheel-running activity mainly followed the food pulses. Under LL conditions, the food-entrained activity consisted mainly of feeding and wheel-running anticipatory activity. The results provide new evidence that lighting conditions influence the establishment and persistence of food-entrained circadian rhythms in rats. The existence of two coupled pacemakers, LEP and FEP, or a multioscillatory LEP may both explain our experimental results.     

Food-Entrained Feeding and Locomotor Circadian Rhythms in Rats Under Different Lighting Conditions

It has been suggested that two endogenous timekeeping systems, a light-entrainable pacemaker (LEP) and a food-entrainable pacemaker (FEP), control circadian rhythms. To understand the function and interaction between these two mechanisms better, we studied two behavioral circadian rhythmicities, feeding and locomotor activity, in rats exposed to two conflicting zeitgebers, food restriction and light-dark cycles. For this, the food approaches and wheel-running activity of rats kept under light-dark (LD) 12:12, constant darkness (DD), or constant light (LL) conditions and subjected to different scheduled feeding patterns were continuously recorded. To facilitate comparison of the results obtained under the different lighting conditions, the period of the feeding cycles was set in all three cases about Ih less than the light-entrained or free-running circadian rhythms. The results showed that, depending on the lighting conditions, some components of the feeding and wheel-running circadian rhythms could be entrained by food pulses, while others retained their free-running or light-entrained state. Under LD, food pulses had little influence on the light-entrained feeding and loco-motor rhythms. Under DD, relative coordination between free-running and food-associated rhythms may appear. In both cases, the feeding activity associated with the food pulses could be divided into a prominent phase-dependent peak of activity within the period of food availability and another afterward. Wheel-running activity mainly followed the food pulses. Under LL conditions, the food-entrained activity consisted mainly of feeding and wheel-running anticipatory activity. The results provide new evidence that lighting conditions influence the establishment and persistence of food-entrained circadian rhythms in rats. The existence of two coupled pacemakers, LEP and FEP, or a multioscillatory LEP may both explain our experimental results.     

Circadian Rhythm of Outside-Nest Activity in Wild (WWCPS), Albino and Pigmented Laboratory Rats

The domestication process of the laboratory rat has been going on for several hundred generations in stable environmental conditions, which may have affected their physiological and behavioural functions, including their circadian system. Rats tested in our ethological experiments were laboratory-bred wild Norway rats (WWCPS), two strains of pigmented laboratory rats (Brown Norway and Long Evans), and two strains of albino rats (Sprague-Dawley and Wistar). Rats were placed in purpose-built enclosures and their cycle of activity (time spent actively outside the nest) has been studied for one week in standard light conditions and for the next one in round-the-clock darkness. The analysis of circadian pattern of outside-nest activity revealed differences between wild, pigmented laboratory, and albino laboratory strains. During daytime, albino rats showed lower activity than pigmented rats, greater decrease in activity when the light was turned on and greater increase in activity when the light was switched off, than pigmented rats. Moreover albino rats presented higher activity during the night than wild rats. The magnitude of the change in activity between daytime and nighttime was also more pronounced in albino rats. Additionaly, they slept outside the nest more often during the night than during the day. These results can be interpreted in accordance with the proposition that intense light is an aversive stimulus for albino rats, due to lack of pigment in their iris and choroid, which reduces their ability to adapt to light. Pigmented laboratory rats were more active during lights on, not only in comparison to the albino, but also to the wild rats. Since the difference seems to be independent of light intensity, it is likely to be a result of the domestication process. Cosinor analysis revealed a high rhythmicity of circadian cycles in all groups.     

Intracerebroventricular injection of ghrelin decreases wheel running activity in rats

There is an increasing interest in elucidating the molecular mechanisms by which voluntary exercise is regulated. In this study, we examined how the central nervous system regulates exercise. We used SPORTS rats, which were established in our laboratory as a highly voluntary murine exercise model. SPORTS rats showed lower levels of serum ghrelin compared with those of the parental line of Wistar rats. Intracerebroventricular and intraperitoneal injection of ghrelin decreased wheel-running activity in SPORTS rats. In addition, daily injection of the ghrelin inhibitor JMV3002 into the lateral ventricles of Wistar rats increased wheel-running activity. Co-administration of obestatin inhibited ghrelin-induced increases in food intake but did not inhibit ghrelin-induced suppression of voluntary exercise in rats. Growth hormone secretagogue receptor (GHSR) in the hypothalamus and hippocampus of SPORTS rats was not difference that in control rats. We created an arcuate nucleus destruction model by administering monosodium glutamate (MSG) to neonatal SPORTS rats. Injection of ghrelin into MSG-treated rats decreased voluntary exercise but did not increase food intake, suggesting that wheel-running activity is not controlled by the arcuate nucleus neurons that regulate feeding. These results provide new insights into the mechanism by which ghrelin regulates voluntary activity independent of arcuate nucleus neurons.     

Risk-sensitive foraging in rats: the effects of response-effort and reward-amount manipulations on choice behavior

The literature on risk-sensitive foraging theory provides several accounts of species that fluctuate between risk-averse and risk-prone strategies. The daily energy budget rule suggests that shifts in foraging strategy are precipitated by changes in the forager's energy budget. Researchers have attempted to alter the organism's energy budget using a variety of techniques such as food deprivation, manipulation of ambient temperatures, and delays to food reward; however, response-effort manipulations have been relatively neglected. A choice preparation using a wheel-running response and rats examined risk-sensitive preferences when both response effort and reward amounts were manipulated. Concurrently available reinforcement schedules (FI/60 and VI/60) yielded equivalent food amounts per unit time in all treatments. Two levels of response effort (20 or 120 g tangential resistance) and two levels of reward amount (three or nine pellets) were combined to form four distinct response-effort/reward-amount pairings. Increasing reward amounts significantly shifted choice toward the FI schedule in both response-effort conditions. The incidence of choice preference and the magnitude of shifts in choice were greater for the high response-effort conditions than for the low response-effort conditions. Implications of the significant interaction between response effort and reward amount are discussed in terms of a general energy-budget model.     

Thirst and salt appetite responses in young and old Brown Norway rats

Male Brown Norway rats aged 4 mo (young) and 20 mo (old) received a series of experimental challenges to body fluid homeostasis over approximately 3 mo. Water was available for drinking in some tests, and both water and 0.3 M NaCl were available in others. The series included three episodes of extracellular fluid depletion (i.e., furosemide + 20 h of sodium restriction), two tests involving intracellular fluid depletion (i.e., hypertonic saline: 1 or 2 M NaCl at 2 ml/kg body wt sc), one test involving overnight food and fluid restriction, and testing with captopril adulteration of the drinking water (0.1 mg/ml) for several days. Old rats were significantly heavier than young rats throughout testing. Old rats drank less water and 0.3 M NaCl after sodium deprivation than young rats, in terms of absolute and body weight-adjusted intakes. Old rats drank only half as much water as young rats in response to subcutaneous hypertonic NaCl when intakes were adjusted for body weight. Old rats drank less 0.3 M NaCl than young rats after overnight food and fluid restriction when intakes were adjusted for body weight. In response to captopril adulteration of the drinking water, young rats significantly increased daily ingestion of 0.3 M NaCl when it was available as an alternative to water and significantly increased daily water intakes when only water was available, in terms of absolute and body weight-adjusted intakes. Old rats had no response to captopril treatment. These results add important new information to previous reports that aging rats have diminished thirst and near-absent salt appetite responses to regulatory challenges.     

Effect of the post-weaning environment on the climbing behaviour of wild and domestic Norway rats

The climbing behaviour of wild and domestic Norway rats (Rattus norvegicus) was compared after early rearing in three post-weaning environments offering different climbing experiences. Wild rats climbed in the test apparatus even when denied early climbing experience; male domestic rats did not. Early climbing experience increased the climbing scores of both stocks but influenced the climbing proficiency of wild rats only. Treatment differences in climbing behaviour may be related to specific motor experiences gained during development and the effect of early experience on the response to a novel environment (test apparatus). Stock differences in climbing behaviour may reflect a general reduction in motor activity among domestic rats and their reduced sensitivity to stimulus change or novelty.     

Role of dorsomedial hypothalamic neuropeptide Y in energy homeostasis

Hypothalamic neuropeptide Y (NPY) is primarily expressed in the arcuate nucleus (Arc) and the dorsomedial hypothalamus (DMH). Although Arc NPY gene expression is responsive to circulating leptin, the regulation of DMH NPY expression is leptin-independent. DMH NPY expression is increased in response to chronic food restriction, but not acute food deprivation. DMH NPY expression is elevated in pair-fed OLETF rats lacking cholecystokinin (CCK)-1 receptors. A role for CCK in controlling DMH NPY expression is demonstrated by the down-regulation of DMH NPY by parenchymal DMH CCK administration in intact rats. Moreover, access to running wheels normalizes body weight and prevents altered DMH NPY expression of OLETF rats. Together, these data suggest that DMH NPY plays an important role in feeding and body weight control.     

Nocturnal to Diurnal Switches with Spontaneous Suppression of Wheel-Running Behavior in a Subterranean Rodent

Several rodent species that are diurnal in the field become nocturnal in the lab. It has been suggested that the use of running-wheels in the lab might contribute to this timing switch. This proposition is based on studies that indicate feed-back of vigorous wheel-running on the period and phase of circadian clocks that time daily activity rhythms. Tuco-tucos (Ctenomys aff. knighti) are subterranean rodents that are diurnal in the field but are robustly nocturnal in laboratory, with or without access to running wheels. We assessed their energy metabolism by continuously and simultaneously monitoring rates of oxygen consumption, body temperature, general motor and wheel running activity for several days in the presence and absence of wheels. Surprisingly, some individuals spontaneously suppressed running-wheel activity and switched to diurnality in the respirometry chamber, whereas the remaining animals continued to be nocturnal even after wheel removal. This is the first report of timing switches that occur with spontaneous wheel-running suppression and which are not replicated by removal of the wheel.     

Induction of voluntary prolonged running by rats

The rat is widely used in studies of the metabolic and physiological effects of physical exercise. The most commonly used form of exercise is running on treadmills or mechanically driven running wheels. Rats will not voluntarily run significant distances, under normal circumstances. If rats are exposed to running wheels with food freely available, only very limited activity normally occurs. When rats with access to a running wheel are restricted to a fixed amount of food, presented once per day, consistent running occurs. The running is spontaneous and very sensitive to the amount of food provided. Six 6-wk-old rats of 197 g mean body wt were induced to run for 139 days. The distance run increased rapidly over a 20-day initial period on a food supply of 15 g/day (vs. 19.5 g/day consumption by sedentary controls). From day 20 to day 139 the mean distance run was described by the regression equation distance (m/day) = 10,410 - 37.9 X days. Food provided was varied according to distance run, ranging from 15 to 18 g/day, and was normally 17.5 g/day. Thus a food deprivation of 10% of normal consumption will result in mean distances run of approximately 8,000 m/day. The use of pair-fed control animals without access to a wheel allows the conduct of experiments to test the effects of chronic long-distance running. The running is spontaneous; thus the technique avoids the complications accompanying techniques that force running.     

CRH and NPY are not decreased in hypophagic, protein-deprived rats

To test if elevated CRH and decreased NPY might account for pituitary-adrenal activity and hypophagia in dietary protein deprivation, rats received normal or protein-free diet, or were food-or weight-restricted to match effects of protein deprivation. Protein or food restriction increased plasma ACTH. However, hypothalamic CRH mRNA was unchanged by protein deficiency and significantly decreased by food restriction when protein intake was > 50% of normal. Arcuate nucleus NPY mRNA increased in rats given protein-free diet, correlating with leptin rather than decreased feeding. We conclude that CRH and NPY gene expression does not explain adrenocortical axis or feeding activity in protein-deprived rats.     

Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-alpha is involved

When food was removed from young rats in the early morning, adipose tissue tumor necrosis factor (TNF)-alpha activity increased 50% and lipoprotein lipase (LPL) activity decreased 70% in 6 h. There was a strong negative correlation between the TNF-alpha and LPL activities. Exogenous TNF-alpha further decreased LPL activity. Pentoxifylline, known to decrease production of TNF-alpha, had no effect on LPL activity in fed rats but almost abolished the rise of TNF-alpha and the decrease of LPL activity in rats deprived of food. The specific activity of LPL decreased from 0.92 mU/ng in fed rats to 0.35 and 0.24 mU/ng in rats deprived of food given saline or TNF-alpha, indicating a shift in the LPL molecules toward an inactive state. Lipopolysaccharide increased adipose tissue TNF-alpha and decreased LPL activity. Both of these effects were strongly impeded by pretreatment of the rats with pentoxifylline, or dexamethasone. Pretreatment of the rats with actinomycin D virtually abolished the response of LPL activity to food deprivation or exogenous TNF-alpha. We conclude that food deprivation, like lipopolysaccharide, signals via TNF-alpha to a gene whose product causes a rapid shift of newly synthesized LPL molecules toward an inactive form and thereby shuts down extraction of lipoprotein triglycerides by the adipose tissue.     

Metabolic and endocrine effects of water and/or food deprivation in rats

Metabolic and endocrine effects of water and/or food deprivation in rats. We aim at studying the effect of water deprivation, food deprivation and their combination for three days on adrenal cortex, pituitary-thyroid axis and vasopressinergic system activity in rats. Corticosterone level was determined by fluorimetric method. The levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were determined by immunoenzymatic assay and vasopressin (AVP) level was determined by radio-immunoassay. In all three groups, basal levels of plasma corticosterone were increased. A thyroid dysfunction was shown after water deprivation, food deprivation and their combination reflected by a significant decrease in FT4 levels. Paradoxically, a significant decrease in TSH level was observed in food-deprived rats and in rats subjected to simultaneous food and water deprivation, while a slight and not significant decrease in TSH level was shown in water-deprived rats. A significant increase in plasma AVP level was observed after water deprivation and simultaneous water and food deprivation, while no change was found after food deprivation. The data indicated that water deprivation, food deprivation and their combination stimulated the adrenal cortex, thereby suggesting a stress state. On the other hand, it seems that nutritional stress modifies the pituitary-thyroid axis through mechanisms different from those of osmotic stress. Moreover, it seems that food deprivation partially prevented the stimulatory effect of water deprivation on vasopressinergic system.     

Responding for sucrose and wheel-running reinforcement: effect of pre-running

Six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. To assess the effect of pre-running, animals were allowed to run for 1h prior to a session of responding for sucrose and running. Results showed that, after pre-running, response rates in the later segments of the 30-s schedule decreased in the presence of a wheel-running stimulus and increased in the presence of a sucrose stimulus. Wheel-running rates were not affected. Analysis of mean post-reinforcement pauses (PRP) broken down by transitions between successive reinforcers revealed that pre-running lengthened pausing in the presence of the stimulus signaling wheel running and shortened pauses in the presence of the stimulus signaling sucrose. No effect was observed on local response rates. Changes in pausing in the presence of stimuli signaling the two reinforcers were consistent with a decrease in the reinforcing efficacy of wheel running and an increase in the reinforcing efficacy of sucrose. Pre-running decreased motivation to respond for running, but increased motivation to work for food.     

Anticipatory activity rhythms under daily schedules of water access in the rat.

Rats anticipate a fixed daily feeding time by entrainment of a component of their multioscillatory circadian system. The range of stimuli capable of entraining this component is little studied. Previous studies suggest that restricted water access is not an effective entrainment stimulus, as measured by general locomotion. The present study re-examined the issue, using two other measures of activity: wheel running and activity at a food-water delivery bin. Rats restricted to 1 hr of water each day in the middle of the light and to food in the 12-hr dark period showed no anticipation of this event in the wheel-running measure, but some rats did show anticipation in the delivery bin activity measure. Rats (bin activity measure only) restricted to 1 hr of water and 1 hr of food separated by intervals of 7, 10, or 12 hr, in either the light or the dark, showed consistent anticipation of food access time but little or no anticipation of water access time. Water access time also did not sustain food anticipatory rhythms in animals whose food-water schedules were reversed. However, deprivation of water or of both food and water for 72 or 90 hr was usually associated with specific increases in bin activity at both the usual feeding and drinking times. Water access, like food, appears to provide cues capable of entraining an anticipatory circadian mechanism. Differences in the type and amount of anticipatory activity preceding these events may reflect differences in the strengths of the two entrainment cues and/or in the activity levels or specific behavioral strategies promoted by hunger and thirst.