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A water-soluble chicken extract is popularly consumed as a traditional health food. The studies made revealed that it could increase the survival time and inhibit the increase of locomotor activity in rats loaded with food-deprived activity stress. The mechanism for this might be related to an elevation of the brain histamine level, and the active ingredient, carnosine, might contribute to this effect.

Although past research has indicated that stress and the accompanying increase in glucocorticoids compromises hippocampal neurons, little is known about the effect of stress on hippocampal glial cells. In the current study, male rats were exposed to activity-stress (A-S) for six days; this comprised housing with an activity wheel and restricted access (1h/day) to food. Physiological data (e.g., relative adrenal and thymus weights, gastric ulceration) suggested that the A-S rats experienced more stress than pair-fed (no wheel) and control (fed ad libitum, no wheel) rats. Whereas stress did not influence the quantitative morphology of glial fibrillary acidic protein (GFAP)-immunoreactive cells, a semi-quantitative analysis revealed that the A-S rats had significantly more (30%) GFAP-immunoreactive cells in the hippocampal CA3 region than the control rats. Based on the present findings, it appears that the hippocampal astrocytic response to chronic stress may be similar to the response found in endangered, or challenged hippocampal environments, such as in ischemia.

In order to investigate the recovery from activity-stress ulcers by ad lib-feeding and/or cessation of running, male Wistar rats were exposed to the activity-stress paradigm, and the rats that revealed hypothermia (their rectal temperature fell below 36 degrees C) were sacrificed either immediately or after several 24 h periods of healing. Rats that were sacrificed immediately after the appearance of hypothermia and those that were exposed to restricted feeding plus cessation of running revealed severe activity-stress ulcers, whereas few ulcers were observed in rats given ad lib-feeding and those that were given ad lib-feeding plus cessation of running. Although no significant differences in relative weights of spleen and thymus were obtained among the different recovery conditions, the relative weights of the adrenal glands were highest in the restricted feeding plus cessation of running group, whereas, the other animals exposed to the activity-stress paradigm showed no differences. These results indicate that activity-stress ulcers recover under conditions of ad lib-feeding within 24 h, but they are not influenced by cessation of running. These data also suggest that organ weights are not affected by any manipulations employed in the present study.

Rats housed in activity wheels (A-W) or hanging cages (H-C) received food restriction to 4 h/day for 15 days. Food was given at fixed times to entrain the feeding entrainable oscillator or at irregular times to prevent entrainment. One half of the rats received food in the light phase, the other half in the dark phase of the light-dark cycle. Food was then reduced to 6 g/day for 4 days for A-W rats or 7 days for H-C rats. Stomachs were removed 24 h after the last meal and the ulcerated area was quantified. Twenty one of 32 A-W rats and 19 of 32 H-C rats had ulcers in the glandular stomach. Ulcers were significantly larger in A-W rats (p0.01). Activity levels (in A-W rats), % body weight loss and terminal body weight (in both groups) were significantly correlated with the area of ulcers. There was no significant time of day effect on the ulcer severity. However, an unexpected finding was that for A-W rats, those fed at fixed times had larger ulcers than those fed at irregular times (p0.01) while H-C rats showed an expected trend in the opposite direction. One possible explanation for this result is that for A-W rats, the reduced food supply at an expected time of day generated a greater stress response than in rats whose feeding time was unpredictable.

The present study investigated the effect of gonadal hormones on activity, food consumption, severity of ulceration, weight loss, and survival duration in male and female rats exposed to the activity-stress (A-S) paradigm. Animals received either sham surgery or gonadectomy and were housed in activity wheels or standard suspended cages. Results indicated that gonadectomized animals were more likely to engage in high running levels in the A-S paradigm; in addition, castrated males developed significantly more ulceration than the other groups. Neither sex nor gonadectomy affected the survival duration of A-S animals.

The mechanisms and applications of the activity-stress (A-S) research paradigm are examined in this article. Past research has reflected the value of this paradigm in the investigation of ulcerogenesis. Evidence is offered to support a theory explaining the excessive running observed in the A-S animals, according to which, animals commence running to increase body temperature after failing to adapt to the restricted feeding regime. Further, excessive running levels are hypothesized to be sustained by reinforcement resulting from increased mesolimbic dopaminergic activity. Finally, parallels between the behavior observed in the A-S animals and some forms of maladaptive behavior observed in humans are discussed.

The phenomena of activity-based anorexia (ABA) and the activity-stress ulcer (ASU) both involve paradigms in which the food intake of rats is restricted and the animals are allowed voluntary exercise in a running wheel. This study determined the susceptibility of male and female rats to ABA and ASU following 25- and 30-percent losses of their original body weights. Male rats reached both weight loss criteria in a fewer number of days than did female rats. None of the male and female rats sacrificed at the 25% weight loss criterion evidenced gastric lesions; 52% of the animals sacrificed at the 30% weight loss criterion had one or more lesions. No gender differences with respect to gastric lesions were observed at the 30% weight loss criterion; however, at both weight loss criteria, females ate and ran more than males. It is concluded that ASUs are a consequence rather than a cause of ABA, and that there is a sexually “dimorphic” susceptibility to ABA but not ASUs. The utility of using a 25% weight loss criterion for defining ABA is also discussed.

Two methods of monitoring the circadian rhythm of activity in rodents: (1) an activity wheel cage, which detects the number of wheel revolutions, and (2) an internal radio transmitter, which records gross motor activity (GMA) of the animal, were compared in both normal circadian cycles and during the development of activity-stress ulcers. Rats were implanted with a biotelemetry transmitter that detected GMA and body temperature (BT) and placed in activity wheel cages. A 12 hour/12 hour light/dark cycle was maintained throughout the experiment. Subjects were subdivided into two groups: (1) unlimited access to activity wheel (AW) cages and (2) locked activity wheel (LW) cages. Following an ad-libitum habituation period, animals were allowed food access for 1 hour/day during the light. In the habituation period, the animals showed higher GMA and BT during the dark phase when housed in AW cages than in LW cages. Both GMA and number of wheel revolutions increased dramatically after the onset of food restriction for the AW animals. There was a deleterious drop in BT in AW animals as the food-restricted period continued and a significant correlation existed between severity of ulcerations and BT. The findings of this experiment demonstrate that the activity wheel imposes an alternation of the circadian cycle, which, in turn, influences rhythmicity through reentrainment. Additionally, in the activity-stress paradigm, a significant drop in BT correlates with severity of ulcerations. A disrupted circadian cycle, involving hypothermia, is proposed as the mechanism underlying the demise of animals in the activity-stress paradigm.

In the present study, 28 pregnant rats were subjected to either light-restraint stress or no manipulation for days 14–21 of the gestational period. At approx. 50 days of age, both male (n = 16) and female (n = 16) prenatally stressed (PS) and control offspring were subjected to the activity stress (AS) paradigm. During this subsequent stress experience, PS rats developed less ulceration than control rats. PS rats also displayed about half the activity of the control animals during the habituation phase of the AS paradigm, prior to the induction of stress. Given this decrease in baseline activity in PS animals, implications of using activity as a measure of emotionality in PS animals are discussed. Several sex differences were also observed; females differed from males in that they 1) exhibited higher activity levels in both the habituation and experimental phases of the AS procedure, 2) developed heavier relative adrenal weights, and 3) reached criteria for sacrifice in fewer days.

To examine the role of the amygdala in the production of gastric ulcers induced by activity-stress, electrolytic lesions were placed in the centromedial (CENT) and medial (MED) amygdaloid nuclei, as well as in the intra-amygdaloid division of the bed nucleus of the stria terminalis (BNST). As compared to sham-operated controls (CONT), gastric ulceration was attenuated in rats with CENT lesions and exacerbated in rats with lesions located in the BNST or MED. Wheel running did not differ significantly between control animals and lesioned rats, but did differ within lesioned groups. Rats with MED lesions ran more than rats with CENT or BNST lesions. Results support the view that the integrity of the centromedial amygdala is critical for the maintenance of the viscera and demonstrate that neurogenic factors contribute to the development of gastric erosions during exposure to activity-stress.

The present study investigated the role of dopamine in the maintenance of behaviors observed in the activity-stress paradigm. In Experiment 1, several doses (0, 0.125, 0.25, 0.50, and 1.0 mg/kg) of the dopamine D2-receptor blocker, pimozide, were administered to rats maintained on an ad lib feeding schedule. Results indicated that 0.25 mg/kg pimozide did not disrupt running activity when compared to control animals. In Experiment 2, injections of either 0, 0.25, or 0.50 mg/kg pimozide were given every 12 hours to rats subjected to the activity-stress paradigm. Although 0.25 mg/kg pimozide had no effect on dark-phase activity, it significantly suppressed light-phase activity and subsequently increased the number of survivors in the paradigm. It was concluded that dopamine plays a role in maintaining high running levels in the activity-stress paradigm.

Rats were given d-amphetamine alone, placebo or d-amphetamine and food. They were then placed in the activity-stress ulcer paradigm, involving continuous access to a running wheel while being fed for only 1 hr. per day. Animals given d-amphetamine only ran more and died significantly sooner than animals in any other group. These rats also displayed significantly more gastric glandular ulcers than rats in any other group. Rats given d-amphetamine and food exhibited increased running but did not die sooner and displayed ulceration comparable to placebo rats. It appears that neither restricted feeding nor increased running wheel activity is a sufficient cause of activity-stress ulcers; rather, the combined interaction. of both of these variables appears to produce the observed gastric damage.

The activity-stress ulcer procedure consists of housing rats in running-wheel activity cages while at the same time, restricting their food intake to 1 hr per day. Male Wistar rats which had been habituated with ad lib feeding to the running-wheel cage environment for 3 days prior to the restricted feeding phase, developed significantly more gastric glandular ulcers and exhibited greater levels of running activity when compared to rats which had been given no habituation experience. Control rats housed in standard laboratory cages but which received the same restricted feeding regimen, developed significantly less stress pathology. Since allowing to rats access to the running-wheel during habituation resulted in enhanced stress pathology, this manipulation is referred to as a “priming effect.” A possible explanation for such a “priming effect” is discussed in terms of procedures which may increase running wheel activity and decrease survival time during the restricted feeding phase of the activity-stress ulcer procedure.

Male Wistar rats were exposed to a 5-day activity-stress procedure wherein animals were housed in running-wheel activity cages and fed for only 1 hr each day (wheel-housed/food-restricted rats). This activity-stress procedure produced marked elevation in levels of the major metabolite of noradrenaline (NA), 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in eight brain regions, while a reduction of NA level occurred in several of these brain regions. These rats also exhibited excessive running activity and developed severe gastric glandular ulcers. Rats fed ad lib and housed in activity cages (wheel-housed/ad lib-fed) and rats housed in standard-individual cages and which received either 1-hr daily feeding (control cage-housed/food-restricted) or ad lib feeding (control cage-housed/ad lib-fed) showed neither significant changes in brain NA metabolism nor gastric ulcers. These results suggest that the interaction of a restricted feeding regimen and an increase running wheel activity caused marked enhancement of NA turnover in several brain regions, which is one of the neurochemical mechanisms underlying the physiological and behavioral changes produced by the activity-stress paradigm.

Rats housed in running wheel activity cages except for 1 hr each day, during which time they were fed in their home cages, revealed more stomach ulceration, a higher level of brain MHPG-SO4, and larger weight changes in the thymus, spleen and adrenal gland, compared to rats housed in running-wheel activity cages and fed 1 hr daily in those same cages. Rats in the latter group showed more stress pathology than did control rats which were housed in standard home cages but which received the same restricted (1 hr per day) feeding schedule. These results did not support the idea that excessive running might occur in response to certain motivational states (e.g., frustration due to restricted feeding). The data suggested that feeding activity-stress rats in their home cages might aggravate the development of stomach ulcers coincident with the organ weight changes and the enhancement of noradrenaline turnover in the brain.

In Experiment 1 the number and size of ulcers resulting from exposure to an activity-stress procedure were inversely related to the length of the pre-stress experience with either 1 hr or 2 hr daily feeding schedules. In Experiment 2, rats housed in group cages during the pre-stress period were more vulnerable to the ulcerogenic effects of the activity-stress procedure. A pellet food or powdered food treatment condition failed to provide significant group differences. Vulnerability to stress-ulcer is discussed in terms of the disparity of the environmental conditions between the acclimation period and the activity-stress period.

Rats were divided into either an active group housed in activity wheels or a control group housed in stationary laboratory cages. Both active and control groups were further divided into groups receiving 1, 2, 3, or 4 meals daily for a total feeding time of 1 hr. Control rats were food-yoked to active animals. Results indicated that active rats fed 1 meal daily developed significantly more ulceration, lost more weight, and consumed less food and water than other groups. The number of daily meals had no effect on the amount of activity. No control animals developed ulcers, although they received the same amount of food. These results suggest that frequent feedings mitigate gastric peptic ulcer formation in rats placed in the activity-stress ulcer paradigm.

Spontaneously hypertensive rats (SHR), Wistar Kyoto (WKY) and Wistar rats were exposed to Porsolt's forced-swimming test of “behavioral despair.” In addition to floating time, which was the measure of despair, headshakes, bobbing, diving and struggling time were also recorded. Rats were subsequently exposed to the activity stress (A-S) ulcer procedure. Wistar rats had the highest struggling time scores and the fewest A-S ulcers. WKY rats were judged as more depressed and their ulcer severity scores were significantly greater as compared to SHR and Wistar rats. In addition, a within strains analysis revealed that WKY rats with high despair scores also had the most severe stress-ulcer scores. These data suggested that stress-ulcer disease may be more prevalent in animals which are prone to depression as defined by the Porsolt test. The value of WKY rats as an animal model to study the relationship between depression and stress ulcer is discussed.

Rats were exposed to daily sessions of either restraint plus cold, forced exercise, or grid shock for one month and then subjected to the ulcerogenic effects of either supine restraint plus cold, or activity-stress. Chronic stress generally protected against stress ulcer but the protection depended on the degree of similarity between the pre-treatment stressor and the ulcerogenic procedure. Pre-treatment with restraint plus cold provided protection which applied not only to supine restraint plus cold but also generalized to activity-stress. Foot-shock pre-treatment did not significantly reduce restraint ulcer but it significantly exacerbated activity-stress ulcer.

Rats housed in activity cages and fed 1 hour daily died before the end of the 21-day experimental period and revealed extensive ulcers in the glandular stomach, whereas food-yoked control rats, not housed in activity cages, did not die and were ulcer-free. Rats demonstrating high running-activity levels under ad lib feeding conditions subsequently revealed a higher incidence of lesions as compared to low-activity rats. Attempts to attenuate activity and lesion incidence by reversing the light-dark cycle failed, but the higher mortality level in rats under the reversed light-dark condition was related to higher activity levels in these rats. Young rats with high activity levels died sooner and had ulcers when compared to older rats with low activity levels. These results suggested that running activity, and not reduced food intake, was critically involved in the development of the activity-stress ulcer.

The present study was designed to investigate the relationship between activity stress, alcohol consumption and ulcer proliferation. Ethanol consuming rats were initially divided into low, medium or high ethanol preferring groups on the basis of daily ethanol intake (g/kg/day). Following a habituation period in activity cages, animals were fed for 1 hr per day. Access to both water and ethanol remained ad lib. Yoked control home cage animals were fed the same amount of food consumed by their wheel-housed partners. This procedure continued until wheel-housed animals died, at which time thwy and their yoked home cage control partners were examined for ulcers. Results indicated that in contrast to the yoked controls, only the high ethanol-preferring rats reduced their ethanol consuption. Although no differences were apparent in ulcer frequency (mean number of ulcers per rat) or severity (mean cumulative ulcer length in millimeters), animals exposed to ethanol had a lower ulcer incidence (number of rats per group developing ulcers) and mortality rate than non-ethanol exposed animals.

Rats sacrificed after 4 days in the activity-stress paradigm or after 4 days of food restriction had significantly elevated levels of plasma corticosterone as compared to control rats. The approximately 5 fold increase in corticosterone in the stressed treatment groups was consistently found in all experiments. ACTH levels were elevated in activity-stress and food-restricted groups in some experiments but these increases were not statistically significant. Prolactin levels were significantly elevated in food-restricted group rats as compared to controls or activity-stress group animals in one experiment but this finding was not repeated in further experiments. In a second series of experiments, rats from activity-stressed and food-restricted treatment groups and controls were exposed to an acute stressor for 15 min prior to sacrifice to assess the effects of prior sustained stress on hormonal responses to an acute stressor. Exposure to 15 min of immobilization or intermittent footshock immediately prior to sacrifice increased plasma levels of corticosterone, ACTH and prolactin in control, foodrestricted and activity-stressed rats. Generally, hormonal responses to the acute stress were similar in all treatment groups. However, in two experiments where the resting levels of corticosterone were especially elevated in the activity-stress group, the acute stress-induced rise in corticosterone was less than that seen for the other two treatment groups. In another experiment, administration of dexamethasone suppressed acute stress-evoked levels of ACTH and corticosterone in control, activity-stressed and food-restricted rats. Thus, rats exposed to 4 days of sustained stress were found to have consistently elevated resting levels of corticosterone. Hormonal responses to acute stress or dexamethasone administration, however, were generally similar in activity-stressed, food-restricted and control rats.

Rats were given either seven or 14 days of experience with either restricted feeding (2 hr/day) or activity (24 hr/day of access to activity wheels with ad libitum feeding). Animals were then subjected to the activity-stress ulcer procedure involving 1 hr/day of feeding and continuous access to running wheels. Neither experience with restricted feeding nor with activity wheels attenuated gastric ulceration, indicating that adaptation did not occur. Rats with either restricted feeding experience or activity experience died faster and exhibited more frequent and more severe stomach damage relative to nonexperienced controls.

Rats were exposed to a fat-supplemented (32.5% beef tallow) diet from weaning until they were 200 g in weight. Half the animals were exposed to the activity stress paradigm consisting of housing in standard activity-wheel cages while restricting their food intake to 1 h each day. Control rats were treated in the same fashion but on a fat-free (0.08%) diet. Fat-supplemented activity-stressed rats exhibited high levels of running wheel activity but less mortality and less gastric pathology than fat-free controls which were exposed to the activity-stress procedure. Ulcers were not observed in home cage housed rats in either diet condition.

Rats housed in activity wheels and fed only 1 hr daily had access to either a 50 μg% nicotine solution, a 500 μg% nicotine solution, or tap water as their drinking solution. Usually rats simply housed in activity wheels with 1-hr daily feeding die within 4 to 12 days and reveal lesions in the glandular stomach. It was hypothesized that nicotine would increase the degree of pathology typically observed in the activity-stress situation. Although results were in the hypothesized direction, differences between groups were not statistically significant.

Eighty rats were housed in standard activity wheel cages and fed for only 1 hr per day. The animals were divided into 10-animal drug groups that received either 0.25, 0.50, 1.0 mg/kg of scopolamine methylbromide, or 0.06, 0.125, 0.250 mg/kg of carbachol, 3 times a day. Two separate 10-animal saline control groups accompanied each drug series. All animals died within 6 days and most demonstrated significant gastric lesions in the glandular fundus of the stomach. All dosages of scopolamine methylbromide significantly reduced the number and severity of gastric lesions and in some cases abolished all signs of stomach pathology. None of the dosages of carbachol significantly affected either the number or degree of gastric ulceration noted in the body of the stomach. These results were interpreted to suggest that the secretion of gastric acid may be an important contributing factor in the formation of gastric ulcers in animals subjected to the activity-stress procedure.

In the rat, activity-stress (A-S) treatment was related to varying degrees of inflammation, goblet depletion, and erosion of the mucosal wall. Young (aged twenty-eight days), and mature (aged seventy days), rats did not differ significantly in terms of overall thinning of the colon wall, however the incidence of hematuria, hemorrhage at fecal bolus sites, mucosal hyperemia and interstitial compression of the mucosal wall was greater for younger animals. These findings suggest that A-S produces both more severe and more acute colonic pathology in young animals. The use of the A-S paradigm as an appropriate route for inducing psychological stress is discussed in terms of its capacity to evoke a somatic stress response as indicated by stereotypical alterations of structure and function of the gastrointestinal and thymicolymphatic system.

Rats which develop lesions after exposure to the activity-stress procedure show a drop in core body temperature. Body temperature and running activity are inversely related, thereby suggesting that excessive running is an attempt at behavioral thermoregulation. However, the restricted feeding schedule does not provide sufficient energy to support the high running activity. Rats placed in a cold environment (7°C) and fed only 1 hr daily also develop stomach lesions but not as extensive as rats housed in activity wheel cages and also fed 1 hr daily. These results suggest that the activity-stress procedure is a high energy demand situation and that subsequent stomach lesions represent a disturbance in energy metabolism.

Rats housed in running-wheel activity cages and fed 1 hr or 2 hr daily exhibited excessive running and subsequently died revealing large stomach ulcers, reduced absolute thymus weight, and an increase in relative weight of adrenal glands. However, two 0.5-hr or two 1-hr daily feedings did significantly reduce ulcer incidence. Control rats for the four feeding schedules did not die, were ulcer free, and did not exhibit the changes in thymus and adrenal weight observed in exprimental rats. These results suggest that the divided daily feeding schedule ameliorates the ulcerogenic and immune processes in activity-stress rats.

Forty rats were housed in standard activity wheel cages and fed for only 1 hr per day. The animals were equally divided into 4 groups that received either saline, 12.5 mg/kg, 25.0 mg/kg or 50.0 mg/kg of metiamide, an H2 receptor antagonist, 3 times a day. All animals died within 11 days and all demonstrated significant gastric lesions in the glandular fundus of the stomach. The 50.0 mg/kg dosage group, however, demonstrated significantly fewer ulcers than the saline animals and the lesions that did occur were significantly smaller than those noted in the control animals. Several hypotheses were offered to explain these results which took into account metiamide's effects on gastric secretion and motor activity. It was suggested that secretion of acid may be an important contributing factor in the formation of gastric ulcers in animals subjected to the “activity-stress” procedure.

The activity-stress procedure, which produces severe stomach ulcers, will also produce degeneration in the descending colon and rectum of the rat. In degenerated areas there was about 50–80 percent reduction in the thickness of the mucosa, and a marked depletion of mucus secreting globlet cells.

Susceptibility to ulceration induced by restraint, restraint plus intermittent shock, and activity stress was studied in 6 week and 18 week old Brattleboro and Long-Evans rats. Older animals developed more glandular ulcers than younger animals with Brattleboro rats having significantly greater ulceration than Long-Evans rats in both conditions. With activity stress, younger subjects developed significantly more glandular ulcers than older subjects; whereas, older subjects developed significantly more nonglandular ulcers than younger subjects. In both instances, the ulceration was significantly greater in Brattleboro rats than in Long-Evans rats. There were significantly high correlations among running behavior, survival time, and the development of glandular ulcers in younger animals exposed to activity stress. The presence of vasopressin, as well as the age of the subject and the nature of the stress, influences the type and degree of stomach pathology induced.

Rats fed 1 hr daily and housed in running-wheel activity cages exhibited excessive running and developed stomach ulcers as compared to food control, body weight control and home cage control rats. In addition to the observed gastric disease, experimental animals had increased bilirubins, decreased glycogen and decreased serum proteins suggesting that hepatic disease played a role in the lethal consequence of exposing rats to the activity-stress procedure. The decreases in liver glycogen and serum glucose suggested that the terminal problem was related to incipient exhaustion of metabolic substrates.

Female rats housed in running-wheel activity cages and fed 1 hr. daily ran significantly more than similarly housed and fed male rats. Male rats survived an average of 10 days, whereas mean survival time for female rats was 7.3 days. Experimental activity rats developed glandular stomach ulcers. Pair fed controls housed in cages without activity wheels were ulcer-free. Among experimental activity rats, there were no sex differences with respect to the number or severity of ulcers.

In Experiment 1, gastric samples were obtained by means of a pylorus ligation procedure on either the first or last day of the activity-stress procedure. Experimental rats had more stomach lesions and showed a drop in gastric acid on the last day collection. In Experiment 2, rats were surgically prepared with gastric cannulas and pyloric cuffs, and first and last day collections were obtained from the same animal. Experimental activity rats revealed more stomach lesions and a corresponding drop in gastric acid on the last collection than did control rats, which thereby suggests that acid was not a significant etiological variable. The destruction of acid-bearing parietal cells or the back diffusion of hydrogen ions could also explain the low acid values in rats with stomach lesions.

Rats, hamsters, gerbils and guinea pigs were housed in activity cages and fed 1 hr each day. By the end of the 21-day experimental period, 86, 100, 70 and 70% of rats, hamsters, gerbils and guinea pigs had developed lesions in the glandular stomach. This procedure was thus capable of producing lesions in species other than the rat, thereby increasing the value of the procedure as an ulcerogenic technique.

Gastric lesions were produced in albino rats by allowing continuous access to a running wheel, but only one hour's access to food each day. A reliable pattern of changes in activity, food intake, and body weight, culminating in severe debilitation, resulted. Animals were sacrificed when food intake fell below 2 g. The glandular stomachs of these rats showed extensive pathology, ranging from mucosal hemorrhage, with or without focal necrosis, through acute ulcers characterized by discontinuity of the muscularis mucosa. With one exception, all experimental rats showed this entire range of pathology, and in addition, 33% had at least one lesion showing signs of regeneration. Focal erosions predominated, but all experimental rats had at least one ulcer penetrating the muscularis mucosa. No control rat had a lesion of any sort.

SummaryYoung male rats fed for 1 hr/day only failed to adapt to restricted food intake and died within a 4-day period. All animals in this group developed extensive gastric ulceration and gastric hemorrhage. When the daily food intake was restricted to 2 hr, none of the animals expired and only 2 showed gastric lesions; no pathologic changes were seen in rats fed adlibitum.The authors appreciate the excellent technical assistance of Mr. Jack Tomlinson.

1. 1. Daily i.p. injections of zinc sulphate significantly reduced the frequency and severity of activity-stress gastric lesions in rats in a dose-related fashion. 2. 2. These lesions are believed to be of a non-acid etiology and respond primarily to centrally-acting agents. 3. 3. The present results suggest that some local factors contribute to activity-stress gastric damage.