Multiple exposure to activity anorexia in rats: effects on eating,weight loss,and wheel running

Animals were given five cycles of an activity anorexia (AA) procedure in order to determine the effect of additional experience on eating, running, and weight loss. Female Sprague-Dawley rats were given a 1h meal and allowed access to a running wheel for the remainder of each day. Upon reaching 75% of free-feeding body weight, each animal was denied wheel access and given ad libitum food until it regained the lost weight. Then, food was again restricted and wheel access provided. Sedentary control animals were placed on the restricted feeding schedule for the median number of days experimental animals required to reach weight loss criterion. Experimental animals showed adaptation by increasing food consumption and decreasing the rate of weight loss despite an increase in running across cycles. Additionally, the distribution of running shifted gradually so that during the later cycles, much of the running occurred in the hours just before feeding. The results support the hypothesis that running interferes with adaptation to the restricted feeding schedule and also that the marked increase in anticipatory behavior during the later cycles is primarily responsible for the maintenance of AA.     

Sex differences in voluntary locomotor activity of food-restricted and ad libitum-fed rats. Implications for the maintenance of a body weight set-point

1. Male and female Wistar-strain rats were studied under either ad libitum or 23-hour food restriction conditions both with and without access to a running wheel. 2. Daily measures were taken of body weight, food consumption and wheel revolutions. 3. It was observed that food restriction was associated with decreased food consumption and body weight but increased wheel revolutions. 4. Irrespective of feeding regime, females exhibited higher running rates than males.     

Daily Changes of Plasma Corticosterone by an 8-h Daytime Feeding Occur Without Body Weight Loss or Severe Food Restriction in the Rat

Different studies have reported that daytime feeding entrains the circadian rhythm of corticosterone secretion in rats. However, it remained unclear whether calorie restriction or daytime feeding access have an effect. The aim of our study is to evaluate the effect of an 8-h daytime feeding access on the circadian rhythm of plasma corticosterone. Eleven adult male Wistar rats were assigned to two different conditions of access to food: ad lib feeding for one week and daytime feeding for the following two weeks. On the 7th, 14th and 21st day, blood samples were collected every 4 h from 08:00 to 04:00. Food intake and body weight were recorded daily. During daytime feeding, rats ingested 88% of the amount of food ingested over 24 h in the ad lib feeding period. However, body weight increased significantly from the first day to the end of experiment. Peak plasma corticosterone was 12 h shifted during daytime feeding period compared to the ad lib condition. This study showed that an 8-h daytime feeding entrained the circadian rhythm of plasma corticosterone without body weight loss or severe food restriction.     

Daily Changes of Plasma Corticosterone by an 8-h Daytime Feeding Occur Without Body Weight Loss or Severe Food Restriction in the Rat

Different studies have reported that daytime feeding entrains the circadian rhythm of corticosterone secretion in rats. However, it remained unclear whether calorie restriction or daytime feeding access have an effect. The aim of our study is to evaluate the effect of an 8-h daytime feeding access on the circadian rhythm of plasma corticosterone. Eleven adult male Wistar rats were assigned to two different conditions of access to food: ad lib feeding for one week and daytime feeding for the following two weeks. On the 7th, 14th and 21st day, blood samples were collected every 4 h from 08:00 to 04:00. Food intake and body weight were recorded daily. During daytime feeding, rats ingested 88% of the amount of food ingested over 24 h in the ad lib feeding period. However, body weight increased significantly from the first day to the end of experiment. Peak plasma corticosterone was 12 h shifted during daytime feeding period compared to the ad lib condition. This study showed that an 8-h daytime feeding entrained the circadian rhythm of plasma corticosterone without body weight loss or severe food restriction.     

The effect of food deprivation on drinking and running in Mongolian gerbils

Three experiments are reported in which adult male Mongolian gerbils (Meriones unguiculatus) were subjected to various degrees of partial food deprivation, with or without simultaneous access to a running wheel. Experiment 1 showed that restricted feeding caused drinking to increase and running to decrease, and it offered no support for the idea that running might substitute for drinking. Experiment 2 showed that running declined, and then at least partly recovered, as a function of body weight loss, in gerbils that were not allowed to become hyperdipsic. Experiment 3 showed that drinking remained at a high level during prolonged exposure to restricted feeding, but reverted to baseline level more rapidly than did body weight when free feeding was reinstated. The results do not support the idea that drinking and running are interchangeable members of a set of activities facilitated by food deprivation, and they show that neither drinking nor running is related to degree of body weight loss in a simple manner.     

Effects of prior or concurrent food restriction on amylin-induced changes in body weight and body composition in high-fat-fed female rats

Amylin infusion reduces food intake and slows body weight gain in rodents. In obese male rats, amylin (but not pair feeding) caused a preferential reduction of fat mass with protein preservation despite equal body weight loss in amylin-treated (fed ad libitum) and pair-fed rats. In the present study, the effect of prior or concurrent food restriction on the ability of amylin to cause weight loss was evaluated. Retired female breeder rats were maintained on a high-fat diet (40% fat) for 9 wk. Prior to drug treatment, rats were either fed ad libitum or food restricted for 10 days to lose 5% of their starting body weight. They were then subdivided into treatment groups that received either vehicle or amylin (100 microgxkg(-1)xday(-1) via subcutaneous minipump) and placed under either a restricted or ad libitum feeding schedule (for a total of 8 treatment arms). Amylin 1) significantly reduced body weight compared with vehicle under all treatment conditions, except in always restricted animals, 2) significantly decreased percent body fat in all groups, and 3) preserved lean mass in all groups. These results indicate that amylin's anorexigenic and fat-specific weight loss properties can be extended to a variety of nutritive states in female rats.     

Effects of food restriction on the length of lactational diestrus in rats

The effect of food restriction (60% of an ad lib ration) for the first 14 days postpartum on serum progesterone levels and the duration of lactational diestrus was determined in rat dams nursing litters of eight pups. Food restricted dams showed a longer period of lactational diestrus than ad lib fed dams. Food restriction also caused an increase in progesterone levels that was maintained beyond the period of food restriction itself. Treatment with the dopamine agonist bromocryptine mesylate (0.5 mg/day) either from Day 1 or Day 9 postpartum onward induced early termination of lactational diestrus in both ad lib and food restricted dams but the effect was more rapid in the ad lib fed than in the food restricted females. In both cases, however, the effects of bromocryptine administration on milk delivery showed a similar time course providing indirect evidence that prolactin suppression was equivalent under both diet conditions. These data suggest that food restriction during lactation results in increased progesterone levels that most likely result from increased prolactin release. Further, while prolactin suppression in food restricted dams reduces the duration of lactational diestrus, the latency to do so is somewhat longer than that seen in ad lib fed females, suggesting that some other mechanism may also be operating to suppress ovulation in the food restricted female.     

Ghrelin mediates anticipation to a palatable meal in rats

Food anticipatory activity (FAA) is displayed in rats when access to food is restricted to a specific time frame of their circadian phase, a behavior thought to reflect both hunger and the motivation to eat. Rats also display FAA in a feeding schedule with ad libitum access to normal chow, but limited availability of a palatable meal, which is thought to involve mainly motivational aspects. The orexigenic hormone ghrelin has been implicated in FAA in rodents with restricted access to chow. Because ghrelin plays an important role not only in the control of food intake, but also in reward, we sought to determine the role of ghrelin in anticipation to a palatable meal. Plasma ghrelin levels of non-restricted rats that anticipated chocolate correlated positively with FAA and were increased compared with chow-fed control rats. Furthermore, centrally injected ghrelin increased, whereas an antagonist of the ghrelin receptor decreased, the anticipation to chocolate. Therefore, we hypothesize that central ghrelin signaling is able to mediate the motivational drive to eat.     

The importance of paternal care on pup survival and pup growth in Peromyscus californicus when required to work for food

We examined paternal care in the monogamous California mouse when wheel running was necessary to obtain food. Paternal and maternal care, pup survival and feeding were compared in litters with single females (Male Absent) and paired females (Male Present) under three different foraging requirements. When wheel running was required for obtaining food (Wheel Contingent), the male's presence significantly increased pup survival. There were no significant effects of the male's presence on pup survival in the No Wheel (standard laboratory housing with ad lib food) or Wheel Noncontingent (running wheel with ad lib food) groups. Males may have indirectly increased pup survival by helping generate food through wheel running and then subsequently spending less time eating than females. While females reduced the time spent in parental care as pups aged, males increased the time spent in parental care as pups aged. Thus as pups became larger and more expensive to rear, the male increased parental care. These results indicate that paternal care benefits pup survival more under conditions where the parents must forage to obtain food than when food is provided ad lib in the standard laboratory environment.     

Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon.

The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise.     

Interaction between exercise and food restriction: effects on longevity of male rats

Male rats that exercise in running wheels have a longer average survival than freely eating sedentary controls but, in contrast to food-restricted sedentary controls of the same weight, show no extension of maximal life span (J. Appl. Physiol. 59: 826-831, 1985). To test the possibility that exercise may counteract a life-extending effect of decreased availability of energy for certain biological processes such as cell proliferation, we examined the combined effects of exercise and food restriction on longevity of male rats. As before, wheel running improved average length of life, 978 +/- 172 vs. 875 +/- 175 (SD) days, for the sedentary controls (P less than 0.01) without increasing maximal life span. Paired-weight controls, food restricted (approximately 30% below ad libitum) to weight the same as the runners, showed increases in both average (1,056 +/- 144 days) and maximal life span. Food-restricted runners, with intake restricted to the same extent (approximately 30%), had an increased mortality rate over the first approximately 50% of their survival curve up to approximately 900 days of age; their average life span (995 +/- 226) was similar to that of the control group of runners and shorter than that of their paired-weight food-restricted sedentary controls (1,088 +/- 159 days, P less than 0.05). However, after approximately 900 days of age the food-restricted runners' survival became similar to that of the food-restricted sedentary groups, with a comparable increase in maximal life span. Thus the exercise did not counteract the increase in maximal life span induced by food restriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats

In operant conditioning experiments, two methods are commonly used to motivate laboratory rats to perform designated tasks. The first is restricting food so that rats are forced to lose 20% of body weight within one week, followed by maintenance at 80% of the baseline weight for the remainder of the experiment. The second is restricting access to water to 15 min in each 24 h period. These methods are effective in motivating the animals. There is, however, little information available on the effects on performance in tests of behaviour that are not related to operant conditioning. In addition, it is not clear if these commonly used methods of food and water restriction will lead to physiological stress as indicated by an elevation of serum corticosterone. Male rats were either food-restricted to reduce and maintain their weight at 80% of baseline weight, or were restricted to 15 min access to water every 24 h. Activity in the open field was significantly greater in food-restricted rats than in water-restricted or control rats, but freezing behaviour was similar in all experimental groups. Food-restricted rats had a higher mean serum corticosterone level than water-restricted and control rats 37 days after the start of the experimental period. These data suggested that chronically restricting food and maintenance of body weight at 80% of baseline body weight led to significant behavioural changes and physiological stress. In contrast, water restriction did not lead to changes in behaviour or corticosterone levels. A second experiment was conducted to compare the effects of food restriction to 80% of baseline body weight, as described above, with a less stringent protocol in which test rats were initially reduced to 80% of baseline weight, but were then maintained at 80% of an ad libitum fed control rat's weight. Serum corticosterone levels and adrenal gland weights were measured after the initial week of forced weight loss and after maintenance for 21 days. Forced loss of 20% of body weight in the first week led to significantly increased serum corticosterone levels and adrenal gland weights compared to ad libitum fed controls. Serum corticosterone levels and adrenal gland weights in rats maintained at 80% of their initial body weight for 21 days remained higher than ad libitum fed control rats. However, rats maintained at 80% of an ad libitum fed control rat's weight did not differ from control rats in serum corticosterone levels or adrenal gland weights at the end of the 21-day study period. Adjustment of the feeding regimen in this manner eliminated physiological evidence of chronic stress.     

Dorsomedial hypothalamic corticotropin-releasing factor mediation of exercise-induced anorexia

Running wheel access and resulting voluntary exercise alter food intake and reduce body weight. The neural mechanisms underlying these effects are unclear. In this study, we first assessed the effects of 7 days of running wheel access on food intake, body weight, and hypothalamic gene expression. We demonstrate that running wheel access significantly decreases food intake and body weight and results in a significant elevation of CRF mRNA expression in the dorsomedial hypothalamus (DMH) but not the paraventricular nucleus. Seven-day running wheel access also results in elevated arcuate nucleus and DMH neuropeptide Y gene expression. To assess a potential role for elevated DMH CRF activity in the activity-induced changes in food intake and body weight, we compared changes in food intake, body weight, and hypothalamic gene expression in rats receiving intracerebroventricular (ICV) CRF antagonist alpha-helical CRF or vehicle with or without access to running wheels. During a 4-day period of running wheel access, we found that exercise-induced reductions of food intake and body weight were significantly attenuated by ICV injection of the CRF antagonist. The effect on food intake was specific to a blockade of activity-induced changes in meal size. Central CRF antagonist injection further increased DMH CRF mRNA expression in exercised rats. Together, these data suggest that DMH CRF play a critical role in the anorexia resulting from increased voluntary exercise.     

Regional Fat Pad Growth and Cellularity in Obese Zucker Rats: Modulation by Caloric Restriction

Objective : To investigate, in young obese male Zucker rats, the effects of chronic food restriction and subsequent refeeding on: 1) parameters of nonadipose and adipose growth, 2) regional adipose depot cellularity [fat cell volume (FCV) and number], and 3) circulating leptin levels. Research Methods and Procedures : Obese (fa/fa) and lean (Fa/?) male Zucker rats were studied from age 5 to 19 weeks. After baseline food intake monitoring, 10 obese rats were subjected to 58 days of marked caloric restriction from ad libitum levels [obese‐restricted (OR)], followed by a return to ad libitum feeding for 22 days. Ten lean control rats and 10 obese control rats were fed ad libitum for the entire experiment. All rats were fed using a computer‐driven automated feeding system designed to mimic natural eating patterns. Results : After food restriction, OR rats weighed significantly less than did lean and obese rats and showed a significant diminution in body and adipose growth as compared with obese rats. Relative adiposity was not different between obese and OR rats and was significantly higher than that of lean rats. The limitation in growth of the adipose tissue mass in OR rats was due mostly to suppression of fat cell proliferation because the mean FCV in each of the four depots was not affected. Serum leptin levels of OR and obese rats were not different from each other but were significantly higher than those of lean rats. Discussion : Marked caloric restriction affects obese male Zucker rats in a manner different from that of nongenetic rodent models (i.e., Wistar rats). In comparison with the response to caloric deprivation of Wistar rats, these calorically restricted obese male Zucker rats appeared to defend their relative adiposity and mean FCV at the expense of fat cell number. These findings indicate that genetic and/or tissue‐specific controls override the general consequences of food restriction in this genetic model of obesity.     

Food restriction and refeeding in growing rats.

1. The interrelationship between food intake, body weight and oxygen consumption was analysed at 25 degrees C in growing rats. 3. The experiment was divided into two phases lasting four weeks each. During the first phase the animals were subjected to energy restriction and during the second phase they were allowed ad lib energy intake. Four groups of rats were studied: Control with ad lib food intake and three restricted groups R4, R5, and R6 which received during the first phase 4, 5, and 6 g per day of stock diet in a single meal. 3. The results showed a decrease in body weight and oxygen consumption during the restriction period and a recovering of the latter during the refeeding period, without body weight recovering. 4. It is concluded that an energy conservation mechanism is present during food restriction and for some time after refeeding.     

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive – running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals’ wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.     

Effects of food restriction and restoration on gonadotropin and growth hormone secretion in immature male rats

This experiment concerned the changing patterns in secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH) under conditions of food restriction and subsequent catch-up growth. Weanling male rats were given either restricted (4 g food/day) or unrestricted access to food until 60 days of age. At this age, food-restricted rats weighed only 25% as much as rats fed ad libitum. Food restriction resulted in a dramatic decrease in the frequency of LH and GH pulses, and in the amplitude of GH pulses. It also slightly but significantly decreased mean blood levels of FSH (which was not secreted in a pulsatile manner in 60-day-old controls fed ad libitum). When restricted rats were given unrestricted access to food, frequency of LH and GH pulses and mean levels of FSH increased significantly and simultaneously within 2 days in half of the animals. Only an additional 8-10% of their body weight decrement was recovered at this time. After 10 days of food restoration, when restricted rats still weighed 50% less than controls, their secretory patterns of all three hormones were not significantly different from those of controls. Thus, recovery of gonadotropin and GH secretion was relatively rapid. Except for the quantitatively lesser impact of food restriction on FSH secretion, there was no evidence of any priorities in the secretion of the three hormones. Under conditions of rapid catch-up growth, the secretory patterns of LH, FSH, and GH appeared to develop simultaneously.     

Cue hierarchies and testicular development: is food a more potent stimulus than day length in an opportunistic breeder (Taeniopygia g. guttata)?

Opportunistic breeders inhabit areas with unpredictable changes in environmental conditions. In such places favorable breeding conditions can occur during any time of year, and one prediction is that individuals should attend to photoperiod less than to more immediate cues to time reproduction. This study tests whether zebra finches utilize photoperiod independently of other proximate cues, specifically food availability. We transferred semi-domesticated male Lesser Sundas zebra finches (Taeniopygia guttata guttata) from 8 h light, 16 h dark per day (8L:16D) with ad libitum food availability to 20L:4D with ad libitum food (LD ad lib group) or food restriction (LD restricted group). A third group remained on 8L:16D with ad libitum food availability (SD ad lib group). Testis volume in LD ad lib males increased and was larger than other groups within 30 and 60 days of photostimulation. By contrast, LD restricted males and SD ad lib males did not exhibit significant gonadal growth. However, both LD groups increased mass irrespective of food availability. Surprisingly, at the end of the experiment the SD ad lib group sang the most undirected song. Our data demonstrate that long days alone are not sufficient to drive reproductive development in this opportunistically breeding species. Rather, it appears that reproductive development is stimulated by extended feeding times or increased food abundance during long days, and not by changes in day length per se. These data lend support to the proposition that photoperiod acts as a supplementary cue or permissive factor in this system, and thus represents the possibility of a reversal in the hierarchy of cue sensitivity.     

Adiponectin is regulated differently by chronic exercise than by weight-matched food restriction in hyperphagic and obese OLETF rats

This study was intended to investigate the effects of chronic exercise on blood adiponectin level. Male Otsuka Long Evans Tokushima Fatty (OLETF) rats (26 weeks old) were divided to undergo either regular 12-week wheel running exercise (EX) or to have food restriction (FR) that resulted in body weight reduction similar to that in EX. Both EX and FR induced similar reductions in body weight, abdominal fat volume and plasma leptin concentration compared with ad libitum control. At the end of the study, although plasma adiponectin level was increased in FR, the adiponectin level did not change in EX. Plasma testosterone level was higher in EX than in either of the other two groups. A significant inverse relationship existed between plasma levels of adiponectin and testosterone for all groups. Our results suggested that 12-week voluntary wheel running exercise induces different effects on plasma adiponectin level than does food restriction, despite similar reduction in body weight, fat tissue mass and plasma leptin concentration. We speculate that the elevated plasma testosterone concentration might offset any hyperadiponectinemic effect of body weight and fat volume reduction in exercising rats.     

Brief refeeding restores reproductive readiness in food-restricted female musk shrews (Suncus murinus)

Food deprivation blocks sexual behavior and disrupts estrous cycles in mammals. We asked whether reduced copulatory behavior, produced by limited food intake, could be reversed by brief refeeding intervals in the female musk shrew. In Experiment 1, animals were food restricted to 60% of ad lib (FR), and an additional group of FR females were refed for 90 min prior to testing (RF). Refed and ad lib (AL) fed females were significantly more likely to mate than FR females. To test the hypothesis that food-induced restoration of copulatory behavior is not the result of changes in peripheral steroids, we repeated Experiment 1 using ovariectomized and testosterone-implanted females. The results from Experiment 2 were similar to those found in the first study. Next, a more severe refeeding schedule was employed; females were restricted to 50% of ad lib intake. Females in the RF and FR groups were significantly less likely than the AL animals to mate. In the last experiment, females were food restricted to 50% and longer refeeding intervals were employed. Four and one-half hours of food intake did not reinstate sexual behavior, but females refed for 12 h were as likely to mate as ad lib fed controls. We also did not detect any differences in plasma concentrations of testosterone and cortisol in AL, FR, and RF ovary-intact animals. These results define a nutritional threshold for copulatory behavior in the musk shrew. Since this species is highly sensitive to small alterations in food intake, it is a useful model for studies of interactions between metabolic fuels and behavior.