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PubMed1995

Curve-shift analysis of self-stimulation in food-restricted rats: relationship between daily meal, plasma corticosterone and reward sensitization.

Chronic food restriction lowers the threshold for lateral hypothalamic electrical self-stimulation (LHSS). This effect has previously been interpreted to reflect a sensitization of reward. In the present study a curve-shift method was used to explicitly differentiate effects of food restriction on brain stimulation rewarding efficacy and performance. Food restriction consistently shifted rate-frequency curves to the left, lowering the M-50 and Theta-0 parameters of rewarding efficacy. Asymptotic rates of reinforcement and slopes of rate-frequency functions were unaffected, confirming that food restriction does not facilitate LHSS by enhancing performance. In this and previous studies, LHSS in food-restricted rats was measured in the period immediately preceding the daily meal when hunger (i.e., period since last meal) and plasma corticosterone are at peak levels. In the light of evidence that corticosterone may regulate sensitivity of the mesolimbic dopamine pathway and account for the sensitizing effect of stress on psychomotor effects of opiates and stimulants, LHSS and corticosterone were measured in the immediate pre-and post-meal periods. While all food-restricted rats displayed elevated corticosterone levels in the pre-meal period and generally displayed a decline to control levels in the post-meal period, the sensitization of reward was not reversed in the post-meal period. These results indicate that chronic food restriction produces a sensitization of reward that does not depend upon the acute state of hunger that precedes the daily meal and does not vary with dynamic changes in plasma corticosterone level.

Animals↗

PubMed1984

Nociceptive thresholds following food restriction and return to free-feeding.

Nine rats were placed on a restricted food diet for 14 days and nociceptive thresholds were measured by the tail-flick procedure. After 24 hr of food restriction nociceptive thresholds increased. This initial increase in nociceptive threshold was followed by a decrease in pain threshold on the second day of food restriction. Nociceptive thresholds returned to pre-deprivation levels on the remaining 11 days of food restriction. When the rats were given free access to food after 14 days of food restriction, nociceptive thresholds increased 24 hr after the reintroduction of food and decreased during the next 24 hr. Thus, the results of the present experiment demonstrate that both food restriction and a return to free feeding after 14 days of food restriction produced the same biphasic pattern of changes in nociceptive thresholds.

Animals↗

PubMed1986

Effects of water restriction on circadian rhythms of corticosterone, growth hormone and thyroid stimulating hormone in adult male rats.

The effects of acute and chronic water restriction on the circadian rhythms of corticosterone, growth hormone (GH), and thyroid stimulating hormone (TSH) were studied in adult male rats. Water restricted rats were allowed to drink between 9:00 and 9:30 a.m. only. Chronic water restriction but not one day of such treatment altered the circadian pattern of corticosterone so that a peak of this hormone appeared before water presentation. In contrast, neither acute nor chronic water restriction altered the qualitative patterns of circadian GH and TSH rhythms although both treatments depressed the secretion of the two hormones, the depression being greater in chronic than in acute water restricted rats. These results indicate that water restriction did not resynchronize the GH and TSH circadian rhythms. It appears that reduced secretion of GH and TSH observed in water restricted rats would be due to the concomitant reduction in food intake.

Animals↗

PubMed1991

Effects of time-restricted access to protein and to carbohydrate in adult mice and rats.

Specific appetites for protein and carbohydrate were investigated by allowing mice and rats time-restricted access to either protein or carbohydrate. Animals were maintained over a period of weeks on a self-selection regimen consisting of three separate macronutrient sources (carbohydrate, fat, and protein). After a baseline phase during which all three diets were freely available, protein-restricted animals were allowed access to the protein diet only during a one-hour period each day, but other diets were always available; access of carbohydrate-restricted animals to the carbohydrate diet was restricted in a similar fashion. Control animals had continuous free access to all three diets throughout the experiment. During the restriction phase, protein-restricted animals showed substantial selective increases in protein intake during the one-hour periods of protein availability, consuming 40-45% of their normal daily protein intake during this phase of the experiment. In contrast, carbohydrate-restricted rats demonstrated no evidence for the development of a carbohydrate appetite, and the carbohydrate appetite of mice was weak and transient. These results are related to current notions concerning specific appetites.

Animals↗

PubMed1991

Haematology and histopathology of seven-week-old broilers after early food restriction.

The haematology and histopathology of seven-week-old broilers were examined after periods of early food restriction, for six, 10 or 14 days from six days old. After several weeks on an ad libitum diet the birds failed to compensate for the weight lost during early food restriction. Immediately after the periods of food restriction, the birds demonstrated significantly increased heterophil/lymphocyte ratios, reduced eosinophils and slightly raised basophil counts. At seven weeks old, a significant reduction was seen in red and white blood cells and thrombocyte numbers together with significant increases in mean cell haemoglobin and mean cell volume. The haematological profile demonstrated a macrocytic normochromic anaemia caused possibly by a folic acid deficiency as a result of the food restriction. Histopathological lesions were seen in the heart, lungs and liver from birds on all diets but there were more lesions the longer the food had been restricted. Lung disease was more marked where there was inadequate ventilation. Cartilaginous and osseous lung nodules were significantly fewer after food restriction. It was postulated that the increase in pathological lesions in the food-restricted birds may be associated with a stress response.

Animals↗

PubMed1992

Effects of exercise and food restriction on rat skeletal muscles.

Studies were undertaken to compare the effects of exercise and food restriction on body weight (BW), muscle weight (MW), muscle fiber size, and proportion of muscle fiber types. 20 male Fischer 344 rats were randomly assigned to four equal groups: ad libitum-fed control (AC), ad libitum-fed exercise (AE), food restricted control (RC) and food restricted exercise (RE). From 6 weeks of age, RC and RE rats received 60% of the daily food intake of AC and AE rats, respectively. At 7 months of age, AE and RE rats began 40-50 min of daily treadmill exercise. Running speed increased from 1.2 to 1.6 miles/hour and the grade increased to 15% during the first 2 weeks of training. After 10 weeks of training, rats were weighed, sacrificed, and the soleus (SOL), plantaris (PLN) and extensor digitorum longus (EDL) muscles were removed at in situ rest length, weighed, and quick-frozen. Standard histochemical assays were performed, and muscle fiber cross-sectional area was determined planimetrically. Training had little effect on MW or BW, but food restriction greatly reduced BW. This resulted in greater MW/BW ratio in RC and RE than AC and AE rats, respectively. Exercise also increased SOL muscle fiber area in ad libitum-fed but not food restricted rats resulting in smaller fibers in SOL of RE than AE. No changes in percentage of SOL fiber types occurred with food restriction or exercise. In PLN, the percentage of fast-twitch oxidative fibers of AE and RE was greater than in AC and RC, but there was no effect of food restriction or exercise on fiber area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

PubMed1990

Herpes simplex virus-specific cytolytic T lymphocytes restricted to a normally low responder H-2 allele are protective in vivo.

The herpes simplex virus (HSV)-specific cytolytic T lymphocyte (CTL) response in C57BL/6 (B6, H-2b) mice is restricted exclusively to the class I major histocompatibility complex (MHC) glycoprotein H-2Kb, with no detectable response restricted by H-2Db. However, analysis of the memory CTL population derived from B10.A(2R) (Kk Db) mice indicated that Db was a functional restriction element, and that failure to detect this subpopulation in B6 mice was not caused by the inability of HSV-derived antigens to associate with this self protein. Two long-term polyclonal CTL lines, one generated from B6 mice restricted by Kb and a second generated from 2R mice restricted by Db, were greater than 99% CD8+ and exhibited no natural killer (NK) cell activity. The adoptive transfer of either CTL line to naive recipients prior to infection in the hind footpads with HSV resulted in reduced levels of virus recovered from footpad tissue during the acute phase of infection and a reduction in latent HSV able to be reactivated from the sensory dorsal root ganglia (DRG) during the latent phase of infection. These results demonstrated not only that HSV antigen(s) may associate with Db, allowing restricted recognition controlled by this H-2 gene product, but also that functional Db-restricted CTL have the potential to exert biological activity in an environment in which they are not normally generated.

Alleles↗

PubMed1980

Modification of mitochondrial respiration by aging and dietary restriction.

Effects of aging and of dietary restriction on mitochondrial recovery and respiratory capacities have been assessed in mice. Old mice (23-26 months) did not differ from adult mice (9-12 months) in amounts of protein recovered in mitochondrial fractions of liver, brain and spleen, but did show a decline in specific activity of cytochrome c oxidase (cyt. c ox.) in liver and spleen. Age effects on in vitro respiration by mitochondria occurred in liver and spleen. In liver, only one substrate (beta-hydroxybutyrate) of four tested was respired at a different rate by old than by young mitochondria. Depression of state 3 respiration and 2,4-dinitrophenol (DNP)-uncoupled rates was observed for this substrate; however, this effect depended on expressing respiration on the basis of mitochondrial protein and was less overt if data were expressed per unit of cyt. c ox. activity. Old spleen mitochondria exhibited a grosser defect, showing a 40% decrease in the respiratory control index (RCI) for (succinate + rotenone)- supported respiration (the only substrate tested) due to a possible increase in state 4 rates. Effects of dietary restriction were assessed in liver and brain of 3-7-month-old mice underfed since weaning. Dietary restriction reduced recovery of total liver mitochondrial protein and liver cyt. c ox. specific activity. Liver mitochondria from restricted mice generally showed increased state 3 rates with no differences from controls in state 4 rates for respiration supported by glutamate or pyruvate + malate, resulting in an increased RCI for these substrates. DNP-uncoupled rates were also raised by dietary restriction. Unlike effects observed in old versus young mice, these differences obtained whether the data were expressed on the basis of mitochondrial protein or on cyt. c ox. activity. Electron microscopy of liver mitochondrial preparations revealed more non-mitochondrial contaminants in old mice and larger mitochondria in dietarily restricted mice. These findings are compatible with reports of age-dependent losses of liver mitochondria and suggest that dietary restriction may retard this loss.

Aging↗

PubMed1989

Effect of chronic food restriction in aging rats. II. Liver cytosolic antioxidants and related enzymes.

The cytosolic status during aging of several antioxidants and enzymatic activities which protect the cell from oxidative damage was explored in the liver of ad libitum-fed and food restricted rats. Restricting calories effectively prevented the age-related decrease in cellular glutathione that occurs in ad libitum-fed rats. Although glutathione reductase exhibited little change with age in ad libitum-fed rats, dietary restriction resulted in greater activity of this enzyme than that of ad libitum-fed animals. Glutathione S-transferase activity of ad libitum-fed rats decreased significantly with age in ad libitum-fed rats but not in food restricted rats. The glutathione peroxidase activity which increased until 12 months in the ad libitum-fed rats declined by 24 months; there was little change with adult age in this enzymatic activity in food restricted rats. Catalase activity declined steadily from 3-24 months in the ad libitum-fed rats, and food restriction prevented this age-related decline. The significance of antioxidants and the related protective enzymes is discussed relative to membrane alterations and the anti-oxidative action of food restriction in relation to age-related degenerative damages.

Aging↗

PubMed1990

Long-term food restriction depresses serum thyroid hormone concentrations in the rat.

Long-term food restriction exerts an anti-aging action in rodents. The mechanism underlying its modulation of aging processes is unknown but changes in endocrine systems have been postulated as couplers of food restriction to aging. The effects of long-term food restriction on the serum concentrations of thyroid hormones were examined in 6-month-old, male Fischer 344 rats. For 4.5 months a Food Restricted group was fed 60% of the amount consumed by an Ad Libitum group. Food restriction did not alter the 24-h mean T4 concentration but reduced the 24-h mean T3 concentration from 95 +/- 1 to 87 +/- 3 ng/dl. The Ad Libitum group exhibited diurnal rhythms in both serum T4 and T3 concentrations, with peak values for each hormone at 1000 h. Although food restriction eliminated the 1000 h peak for both thyroid hormones, it abolished the diurnal variation only for T3. The dietary-induced changes in serum T4 and T3 are consistent with a role for these hormones in the anti-aging action of food restriction.

Aging↗

PubMed1988

Recovery of rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) from body weight restriction: effect of duration of postoperative prerestriction period.

The present study was performed to see whether somatic and underlying metabolic-adaptive responses of DMNL rats and sham-operated controls (CON) to body weight restriction and subsequent refeeding could be influenced by the duration of ad lib feeding between lesion production and start of restriction. In contrast to previous studies (42 and 55 days, respectively) this time was reduced to 25 days. Restriction was similar, i.e., 27 days. DMNL rats show the same adaptive capacity in most parameters as do restricted CON. However, this response was at a lower level of absolute body weight, appropriate, so it appears, for their DMNL-induced lower body weight. In some parameters different responses were noted, however, suggesting that the time of ad lib feeding following the DMNL does indeed affect adaptive responses. Notably, this is the case in both DMNL and CON commensurately. Linear growth was reduced by restriction in the present but not in the two previous studies. Food intake showed a pronounced "overshoot" on refeeding but did not previously. Efficiency of food utilization was normal in the present study but depressed previously. A rise in plasma free fatty acids was not evident but was so in previous experiments. We concluded that, although DMNL rats respond to food restriction and recovery like similarly-treated CON, the duration of the ad lib feeding before restriction and/or the absolute age of the animals at that time, do indeed affect some parameters. This may be related to the fact that different aspects of the DMNL syndrome declare themselves in a sequential rather than a simultaneous manner.

Adipose Tissue↗

PubMed1988

The effect of dietary restriction on mouse T cell functions.

Forty percent dietary restriction on 9-weeks-old C3H/He mice caused decrease of the weight of central lymphoid organs in parallel with the reduction of body weight. However, the percentage of splenic T cells was dramatically increased in diet-restricted mouse spleen cells. Generally, normal mouse spleen cells contained about 30% of Thy 1.2+ T cells, but the restricted mouse spleen cells contained 80% Thy 1.2+ T cells. Ly 1+, L3T4+ T cells, but not Ly 2+ T cells, also increased in diet-restricted mouse compared with the unrestricted mice. In parallel with the dramatic changes of splenic T cells, spleen cells obtained from diet-restricted mice showed higher immunological responses against alloantigen and interleukin 2. It was also demonstrated than nylon-passed splenic T cells obtained from diet-restricted mice showed higher levels of T cell responses against r-IL-2 and alloantigen, indicating that dietary restriction modulates T cell functions themselves.

Animals↗

PubMed1992

Is the establishing of tolerance to self obligatorily MHC restricted?

The prevailing paradigm used to interpret how T cells recognize antigen treats antigen processing as obligatory because the T cell antigen receptor complex can only detect antigen located in a "groove" found on MHC-encoded restricting elements. The vast majority of experimental systems used to analyze how T cells recognize antigen depend on induced T cells executing their effector functions, and it is agreed without exception that this event is MHC restricted. However, to date, the extrapolation of the obligatory MHC restriction of effector function to the level of the antigen-responsive T cell that makes the tolerance induction decision, depends not on experiment, but on theoretical constructs. The few experiments designed to test whether tolerance is MHC restricted are open to several interpretations, only one of which is consistent with the view that all antigen recognition events must be MHC restricted. If it can be shown that tolerance is not obligatorily MHC restricted, then the pillar of the prevailing paradigm will have fallen. The experiments described here throw into serious doubt the evidence that has been used to conclude that tolerance is obligatorily MHC restricted.

Animals↗

PubMedDate not supplied

Modulatory effects of vasopressin on glucose and protein metabolism during food-restriction stress.

Plasma levels of glucose and urea nitrogen were compared in vasopressin-containing (LE) and vasopressin-deficient (DI) rats under ad lib and food-restricted conditions. In the ad lib situation, DI and LE rats had similar levels of glucose and urea nitrogen. Variations in this pattern were observed under food-restricted conditions. The DI animals exhibited lower levels of glucose and higher levels of urea nitrogen than their LE counterparts. During food restriction, the glucose levels of LE animals were not different from that observed under ad lib conditions. A significant decrease, however, was observed in the glucose levels in DI animals during food restriction. Urea nitrogen levels in LE animals decreased during food restriction as compared to the ad lib situation, whereas urea nitrogen levels of DI animals increased during food restriction. These observations indicate that vasopressin has a modulatory role on glucose and protein metabolism during the stress of food restriction.

Animals↗

PubMed1984

Antigen-specific T cell clones restricted by DR, DRw53 (MT), or DP (SB) Class II HLA molecules. Inhibition studies with monoclonal HLA-specific antibodies.

T lymphocyte clones (TLCs) specific for Chlamydia trachomatis were obtained after limiting dilution of activated T cells from a single donor, BS (HLA-A3; B7,15; DR1, 4; DRw53; DPw4). Most of the proliferative TLCs obtained apparently used restriction elements on DR1 or DR4 molecules, expressed in the antigen-presenting cells (APC). The restriction pattern of two TLCs, however, closely followed the DRw53 specificity, while one TLC seemed to be restricted by elements on DPw4 molecules. A panel of murine monoclonal antibodies (Mabs) was employed to further dissect the restriction specificities. The proliferative capacity of some of the TLCs was studied with and without Mabs directed against different HLA molecules, using non-T cells, monocytes, and peripheral blood dendritic cells as APC. Two Mabs, 7.2 and D-54, which seem to detect monomorphic determinants on HLA-DR, inhibited both DR- and DRw53-restricted TLCs. One Mab, 109d6 which reacts with DRw53 determinants, selectively inhibited the DRw53-restricted TLCs. The DP-restricted TLC was not inhibited significantly by any tested Mabs, including two Mabs with putative specificity for monomorphic determinants on the DP molecule.

Antibodies, Monoclonal↗

PubMed1993

Effect of restricted caloric intake on the development of the azoxymethane-induced glutathione S-transferase placental form positive hepatocellular foci in male F344 rats.

The modifying effect of 30% caloric restriction on the occurrence of azoxymethane (AOM)-induced glutathione S-transferase placental form (GST-P) positive hepatocellular foci was investigated in male F344 rats. Starting at 5 weeks of age, groups of animals were fed ad libitum a high-fat (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were s.c. injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). Four days after the second injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) consumed by the ad libitum group, but received the same amounts of fiber, vitamins and minerals. Thirty-two weeks after AOM injections, all animals were necropsied and livers were sectioned and stained for GST-P by a immunohistochemical technique for quantitative analysis of enzyme altered foci of the liver. Comparing AOM treated groups. The density and the unit area of enzyme altered foci were significantly lower in the calorie-restricted group (3.84 +/- 1.55/cm2, 7.96 +/- 5.43%) than in the ad libitum group (10.14 +/- 3.62/cm2, 28.11 +/- 12.33%). The size of foci was also reduced in the calorie-restricted group (17.15 x 10(-3) mm2 vs. 32.36 x 10(-3) mm2). The incidence and density of hepatocellular foci in rats fed calorie restricted diet were significantly lower than those in rats fed ad libitum, comparing vehicle-treated groups. These results indicate that calorie restriction inhibited the occurrence of both of spontaneous and AOM induced GST-P positive foci in rats.

Animals↗

PubMed1994

Combined chronic low dose radiation-caloric restriction: a model for regression of spontaneous mammary tumor.

PURPOSE: This study was carried out to determine whether chronic low dose radiation can act alone or in synergy with restricted diet in down-regulating spontaneously occurring mammary tumor in tumor-susceptible female C3H/He mice and whether immune cells are involved. METHODS AND MATERIALS: At 7 months of age, one-half of the experimental mice were maintained on an ad lib diet, and the other half was adapted over a period of 1 month to a diet of 70% of the daily amount of food consumed by the ad lib-fed mice. The food of the restricted diet was enriched such that the vitamin and mineral intake was the same for both groups. Half of the mice in each group was then subjected to chronic low dose radiation (0.04 Gy per exposure from a 60Co source, 3 x-per-week for 4 weeks) and the other half was sham irradiated. The 70% calorically restricted diet was maintained throughout the study. RESULTS: Chronic low dose radiation alone was ineffective in down-regulating spontaneous mammary tumor, unlike caloric restriction. However, chronic low dose radiation when combined with caloric restriction promoted regression of mammary tumors, which were infiltrated with massive numbers of CD8+ T cells. These phenomena were not seen in mice subjected to caloric restriction alone. CONCLUSION: Combined chronic low dose radiation-caloric restriction appears to be a useful model for promoting spontaneous mammary tumor regression.

Animals↗

PubMed1993

Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamic correlations and prognostic implications. Heart Muscle Disease Study Group.

OBJECTIVES: This study was undertaken to evaluate the frequency of restrictive left ventricular filling pattern in dilated cardiomyopathy, as well as its clinical and hemodynamic correlations and prognostic implications. BACKGROUND: In dilated cardiomyopathy, as in other heart diseases, different left ventricular filling patterns were observed on Doppler echocardiography. Some patients showed a "restrictive filling pattern," similar to that associated with restrictive cardiomyopathy, characterized by predominant E waves and a shortened E deceleration time. METHODS: Pulsed Doppler transmitral curves were analyzed in 79 consecutive patients with dilated cardiomyopathy assigned to two study groups according to E deceleration time: group 1 (n = 36) had a restrictive left ventricular filling pattern (E deceleration time < 115 ms); group 2 (n = 43) had an E deceleration time > or = 115 ms. RESULTS: Patients in group 1 were significantly younger, in a higher New York Heart Association functional class, more frequently had a third heart sound and had a higher left ventricular filling pressure at catheterization. In addition, they showed more severe left and right ventricular dysfunction and dilation, a larger left atrium and more severe mitral regurgitation. A restrictive filling pattern was associated at Doppler study with a higher E wave velocity, lower A wave velocity and higher E/A ratio. During a follow-up interval of 22 +/- 14 months, all 14 patients who subsequently died or required heart transplantation showed a restrictive left ventricular filling pattern. At multivariate analysis, E deceleration time was the most powerful independent prognostic indicator of poor outcome or transplantation. CONCLUSIONS: Restrictive left ventricular filling pattern is frequent in dilated cardiomyopathy, is associated with more severe disease and is a powerful indicator of increased mortality risk and need for heart transplantation.

Adolescent↗