Forced Running Research Articles

Combined forced running stress and subclinical paraoxon exposure have little effect on pyridostigmine-induced acute toxicity in rats.

Pyridostigmine is a short-acting inhibitor of cholinesterase (ChE) used as a pretreatment against potential nerve agent exposure during the Persian Gulf War. As pyridostigmine contains a quaternary ammonium group, it is generally believed to elicit changes in the peripheral nervous system function only. It has been hypothesized, however, that the neurotoxicity of pyridostigmine may be altered by either stress or combined exposures to other toxicants. We evaluated the effects of forced running stress, exposure to the organophosphate anticholinesterase paraoxon, or a combination of both on the acute neurotoxicity of pyridostigmine. ChE (blood, diaphragm, and selected brain regions) and carboxylesterase (CE; liver, plasma) inhibition was also evaluated. Young adult male Sprague-Dawley rats were either given vehicle or paraoxon (0.1 mg/kg, i.m.) and subsets placed in their home cage or forced to run on a treadmill for 60 min. Pyridostigmine (0, 10 or 30 mg/kg, p.o.) was given 60 min after paraoxon dosing and rats were evaluated for cholinergic toxicity just prior to sacrifice 60 min later. No signs of toxicity were noted following paraoxon exposure while both dosages of pyridostigmine (10 and 30 mg/kg, p.o.) elicited signs of functional toxicity. Toxicity was not different with combined paraoxon-pyridostigmine exposures and forced running did not influence toxicity under any conditions. Paraoxon (0.1 mg/kg, i.m.) caused moderate (23-46%) ChE inhibition in blood, diaphragm and brain 2 h after exposure. Pyridostigmine (10 or 30 mg/kg, p.o.) caused extensive inhibition of blood (88-94%) and diaphragm (75-85%) ChE activity but no significant effect on brain regional ChE activity. Forced running stress did not influence the degree of tissue ChE inhibition following either paraoxon, pyridostigmine or paraoxon-pyridostigmine combined exposures. CE activities were inhibited (26-43%) in plasma and liver by paraoxon but inhibition was not influenced by either stress or combined paraoxon-pyridostigmine exposures. These results suggest that subclinical paraoxon exposure and forced running stress, by themselves or in combination, have little effect on acute pyridostigmine toxicity in rats.

Neither forced running nor forced swimming affect acute pyridostigmine toxicity or brain-regional cholinesterase inhibition in rats

Stress-induced change in the distribution of the drug pyridostigmine (PYR) has been proposed as a contributing factor to unexplained illnesses in Persian Gulf War veterans. We evaluated the effects of two stress models, forced running and forced swimming, on acute PYR (30 mg/kg, p.o.) toxicity and cholinesterase (ChE) inhibition in the blood and selected brain regions of young adult male Sprague–Dawley rats (6 weeks of age). Plasma corticosterone levels were measured at 0, 1 and 3 h after termination of forced swimming or forced running to confirm the induction of stress. PYR was given either immediately before stress (15 min swimming; 20 min running) or immediately after stress (15 min swimming; 90 min running) and cholinergic toxicity and ChE inhibition were evaluated at 1, 2 or 4 h after PYR exposure. Additionally, rats were subjected to either swimming (15 min) or running (90 min) stress, anesthetized, injected with horseradish peroxidase (HRP, 100 mg/kg, transcardial) and brain-regional HRP activity measured as an indicator of altered blood–brain barrier integrity. Both forced swimming and forced running resulted in significant elevations of plasma corticosterone levels. PYR caused cholinergic toxicity at all time-points evaluated. Swimming and running stress had little influence on expression of PYR-induced toxicity, however. Blood ChE activity was generally inhibited 77–91% at 1–4 h after PYR, but rats pretreated with PYR prior to forced swimming showed lesser inhibition (64%) 1 h after dosing, possibly because of swimming-induced hypothermia and delayed absorption of the drug. Minimal changes in ChE activity were noted in frontal cortex, cerebellum and hippocampus following PYR exposure (maximal inhibition 28%), and neither swimming nor running stress affected the degree of inhibition. Neither stress model increased HRP accumulation in any brain region. The results suggest that stress associated with forced running or forced swimming has little effect on acute PYR toxicity, entry of PYR into the brain or PYR-induced brain-regional ChE inhibition.

Both Neuropeptide Y and Serotonin Are Necessary for Entrainment of Circadian Rhythms in Mice by Daily Treadmill Running Schedules

This study investigated the role of the suprachiasmatic nucleus (SCN) circadian pacemaker and its neuropeptide Y (NPY) and serotonin (5-HT) afferents in entrainment (synchronization) of mouse circadian rhythms by treadmill running. Blind C57BL/6j mice were run in treadmills for 3 hr/d for 3-10 weeks after receiving radio-frequency lesions of the SCN or the intergeniculate leaflet (IGL, the source of SCN NPY) or infusions of the 5-HT neurotoxin 5,7-DHT into the SCN area. Of 25 intact mice, 22 entrained and three showed period (tau, the mean duration of the circadian cycle) modulations to scheduled running. Arrhythmic SCN-ablated mice did not synchronize to scheduled running in a way suggestive of circadian pacemaker mediation. Of 15 mice with IGL lesions, only two with partial lesions entrained. Mice with complete IGL lesions (five), confirmed by immunocytochemistry, showed no entrainment or tau changes. Of 19 mice with 5-HT lesions, only two with partial lesions entrained. All but two mice with complete (10) or nearly complete (4) 5-HT denervation, confirmed by immunocytochemistry, showed tau modulations during the treadmill schedule. Failure to entrain was not explained by group differences in tau before the treadmill schedules. The results indicate that the SCN and both NPY and 5-HT are necessary for entrainment to 24 hr schedules of forced running but that complete loss of 5-HT does not prevent modulations of pacemaker motion by behavioral stimuli. Treadmill entrainment in mice may involve synergistic interactions between 5-HT and NPY afferents at some site within the circadian system.

Environmentally induced changes in peripheral benzodiazepine receptors are stressor and tissue specific

The stress-induced changes in peripheral benzodiazepine receptors (PBR) can be observed in a number of different tissues, depending upon the nature and chronicity of the aversive experience. In addition, virtually all stress procedures that cause rapid changes in PBR simultaneously increase the physical activity or metabolic rate of the subjects. The present study analyzed the contributions of rapid alterations in activity or metabolic rate with and without aversive stimulation and their subsequent impact on PBR. Mechanically induced increases in activity by forced running stress results in a significant reduction in [ 3H]Ro 5-4864 binding to PBR in olfactory bulb, opposite to the PBR changes in this tissue following forced cold-water swim stress. Pharmacological induction of increased locomotor activity as well as metabolic rate by d-amphetamine causes a significant increase in cardiac PBR binding, again, opposite to the response typically observed following inescapable shock stress. Finally, administration of the anxiogenic beta-carboline, FG-7142, causes increases in both hippocampus and adrenal gland PBR binding reminiscent of acute noise stress exposure. These experiments demonstrate that increased locomotor activity or metabolic rate alone is not a necessary and sufficient condition for previous stress-induced changes in PBR. Conversely, increased metabolic rate coupled with an aversive stimulus appears to be an important factor for inducing stress-like changes in PBR. This data, coupled with previous reports, suggests that rapid alterations in these sites are Stressor and tissue dependent. Finally, we propose that the PBR may be involved in many aspects of the stress response including: a) a biowarning system in adrenal gland, b) participation in stress-induced hypertension via renal PBR, and c) a modulator of stress-induced immunosuppression and subsequent recovery of function or recuperation by actions on immune cells.

Effects of exercise on immune functions in mice

This study was carried out to examine the effects of forced running exercise on the immune functions of male ICR mice. Mice aged 4 weeks were divided into two groups: a non-exercise group (control) and a group given forced running exercise (exercise group). The exercise applied was forced running at 15m/min on a flat floor without any slope for 60 min a day. The duration of exercise was 5 days per week for 12 weeks. The results obtained were as follows: 1) After 12 weeks of forced running exercise, the weight of the anterior tibialis muscle and succinate dehydrogenase activity in the anterior tibialis muscle increased significantly (p < 0.01) in the exercise group compared with the control group. A tendency for thymus weight to increase was shown in the exercise group, and liver and spleen weights were significantly (p < 0.01) greater than in the control group. 2) The potentiation of phagocytic function of the reticulo-endothelial system, examined by the carbon clearance method, was seen in the exercise group. 3) The ability of peritoneal macrophages (M phi) to phagocytose latex beads significantly increased (p < 0.01) in the exercise group. The acid phosphatase activity of peritoneal M phi remained in both groups. However, lactate dehydrogenase activity of peritoneal M phi significantly increased (p < 0.01) in the exercise group compared with the control group. 4) The proliferation of splenocytes induced by Con A in the exercise group significantly increased (p < 0.01) compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exercise in the growing stage in mice and of Astragalus membranaceus on immune functions

A study was carried out to examine the effects of forced running exercise in the growing stage in male ICR mice and of Astragalus membranaceus (As) on their immune functions. The mice were divided at 4 weeks of age into 4 groups. The first group of mice received forced running exercise (E-group), the second group was given As (As-group), the third group received the forced running exercise and was given As (E+As-group) and the fourth group was a control receiving no treatment. The exercise received was forced running at 15 m/min on a flat floor without any slope for 60min a day. The mice of groups E and E+As were exercised 5 times a week for 12 weeks. The mice of groups As and E+As were given As p. o. at 200 mg/kg per day (5 days/week) for 12 weeks. The results obtained were as follows: 1. After 12 weeks of forced running exercise, the weight of the anterior tibialis muscle and succinate dehydrogenase activity in the anterior tibialis muscle increased significantly in groups E and E+As compared with the control group. Thymus weight showed a tendency to increase in groups E and E+As as compared with the control group. 2. The potentiation of the phagocytic function of the reticuloendothelial system examined by the carbon clearance method was seen in groups E, As and E+As. 3. Superoxide anion production of peritoneal macrophages significantly increased in groups As and E+As, but not in group E. 4. The acid phosphatase activity of peritoneal macrophages in groups E, As and E+As significantly increased compared with the control group. 5. Interleukin 1 production by macrophages remained in all groups. 6. The proliferation of splenocytes induced by Con A in groups E, As and E+As significantly increased compared with the control group. These results suggested that forced running exercise in the growing stage in mice and the administration of As enhanced immune functions and that they might also intensify the functioning of the host defense system.

Individual variation in locomotor behavior and maximal oxygen consumption in mice

Individual differences in open-field activity and emotionality (number of defecations and urinations), voluntary wheel running, voluntary and forced maximal sprint running speed on a photocell-timed racetrack, swimming endurance, and maximal oxygen consumption ( V ̇ O 2 max ) were studied in 35 random bred male ICR mice. With the exception of latency in the open field and voluntary speed on a racetrack, all measurements were significantly repeatable on two successive trial days. Maximal oxygen consumption (corrected for body size) was positively correlated with amount of wheel running during each day of a 7-day test, and the correlation became stronger throughout the testing period; however, none of the daily correlations reached statistical significance. The first factor from a principal components (PC) analysis showed positive loadings (component correlations) for all measures of speed in the open field, for both voluntary and forced maximal speeds on the racetrack, and for V ̇ O 2 max , but a negative loading for emotionality. Wheel running and V ̇ O 2 max loaded positively on PC 2. Only swimming endurance loaded strongly on PC 3; this trait was uncorrelated with any other measure of physiology or behavior. These results suggest that measures of both voluntary and forced locomotor speed, as well as amount of voluntary wheel running, may be related to aerobic physiological capacities in untrained mice.

Electrophysiological evidence for axonal degeneration of locus coeruleus neurons following long-term forced running stress

Using electrophysiological methods, a change in the density of axon terminals of locus coeruleus (LC) neurons in the cerebral cortex of rats following long-term forced running stress was examined. The stressed animals were classified into two groups based on spontaneous running activity (SRA) measured for 2 weeks after the stress treatment: 1) animals showing early restoration of SRA (poststress active rat) and 2) animals showing little or no SRA (poststress inactive rat). To quantify the density of LC axon terminals in the cerebral cortex, the percentage of LC neurons antidromically activated by cortical stimulation (projection index, P-index) was assessed. The P-indices for the cortex decreased in the poststress inactive rats. Since the threshold currents for antidromic activation were not altered by the stress treatment, the observed change was considered to reflect a change of the density of LC axon terminals rather than physiological consequences. Therefore, when animals receive a prolonged, severe stress, LC neurons in a certain group of the animals may cause axonal retraction or degeneration in the cerebral cortex.

Tyrosine Hydroxylase Activity in Discrete Brain Regions of Depression Model Rats

Tyrosine hydroxylase (TH) activity was measured in discrete brain regions of rats during short-term forced running stress (FRS). TH activity was also determined in a depression-like state and in a recovered state after a long-term FRS. Under the short-term FRS, the TH activity showed a significant increase in the locus ceruleus, certain limbic regions and tuberoinfundibular system. In the depression-like state, however, there was a significant decrease in the locus ceruleus and certain limbic regions, but a significant increase was seen in the median eminence. The TH activity in recovered rats showed no difference from the level in the controls. These findings demonstrate an adaptive increase in the TH activity in relation to stress, and may also indicate a failure of adaptation in the depression-like state.

Degenerative changes of the rat arcuate nucleus and locus coeruleus by forced running stress

Degenerative changes of the rat arcuate nucleus and locus coeruleus by forced running stress

Degenerative changes of the rat arcuate nucleus and locus coeruleus by forced running stress

Degenerative changes of the rat arcuate nucleus and locus coeruleus by forced running stress

ACTH, prolactin, corticosterone and pituitary cyclic AMP responses to repeated stress

The present experiment was conducted to determine whether the plasma hormonal and pituitary cyclic AMP responses observed following a single exposure to an acute stressor would diminish following reexposures to the same stressor. Fifteen-min stress exposures (forced running) were separated by 45-min recovery periods. Separate groups of control and stressed animals were sacrificed before and after each of four 15-min stress periods and after each recovery period. The first exposure to 15 min of forced running raised plasma ACTH, corticosterone and pituitary cyclic AMP levels approximately 6-fold and more than tripled levels of plasma prolactin. Plasma ACTH and pituitary cyclic AMP responses to the second, third and fourth stress exposures were very similar to the responses to the first stress exposure, and levels of these substances returned to prestress levels during each 45-min recovery period. Plasma prolactin responses to the four stress sessions were somewhat variable but no significant trend among the responses was seen. Plasma prolactin levels also returned to prestress levels between stress exposures. Corticosterone levels were similar following each of the four stress sessions but levels remained elevated compared to prestress levels between stress exposures. These data suggest that pituitary responses to acute stress are rapid, that return to prestress levels is also rapid, with the exception of corticosterone, and that repeated responses of the same magnitude may be evoked when stressors are separated by short recovery periods.

Effect of forced running on rat skeletal muscle with acrylamide neuropathy

This study was performed to evaluate the effect of prolonged forced running on rat lower limb muscles with acrylamide neuropathy. Twenty-four 4-week-old rats were divided into three groups of eight rats. Acrylamide was given to two groups of sixteen rats to induce mild paralysis. Eight rats with acrylamide injections were forced to run 3,200 m/day on a treadmill for five weeks. Running activities slowed the rate of body weight gain and aggravated paralysis. Although the wet weight of tibialis anterior (TA) and extensor digitorum longus (EDL) muscles was reduced by running, that of soleus (SOL) muscles was unchanged. The ratio of their weight to their body weight (BW) remained constant regardless of exercise. Protein content (PC) of muscles was not altered by exercise, either. We postulated that exercise-induced worsening of paralysis in acrylamide neuropathy rats was not caused by muscle pathology. Deterioration of neuropathic condition due to exercise was suggested.

Bending strength of the rat femur as influenced by running exercise and diet program.

Effects of forced running exercise and dietary programs on bending strength and ash content of the femur were studied in forty growing male rats. They were divided into six experimental groups with three levels of feeding and three levels of daily exercise. The forced exercise groups were trained to run on a treadmill at a maximum speed of about 40m/min. Biomechanical data were collected by a three points bending test on intact femora. The food intake restriction caused a marked negative effect on the ultimate bending moment without any influence on the ultimate bending stress. An opposite effect in the bending stress and ash content was observed for two different exercise amount. The moderate exercise amount tended to increase the bending stress and the ash content irrespective of the nutritive condition while the hard exercise amount had a marked negative effect on these variables.

Cingulotomy in the rat fails to block opiate withdrawal effects but elevates stress-induced plasma beta-endorphin

1. 1. Male, albino, Sprague Dawley rats underwent surgical Cingulotomy or sham opperatiqn and were then implanted with subcutaneous morphine pellets or exposed to forced running. 2. 2. The conditions of Cingulotomy or forced running alone did not cause a significant increase in plasma i.r. Beta endorphin concentrations. 3. 3. The combined treatment of Cingulotomy plus forced running caused a significant elevation of plasma β-endorphin concentrations. 4. 4. The cingulum is involved in the elicitation of stress hormone responses in the rat.

Cross-sectional properties along the diaphysis of the rat femur as influenced by forced running exercise.

Cross-sectional properties along the diaphysis of the rat femur as influenced by forced running exercise.

Effect of forced running stress on neuron ultrastructure in the rat arcuate nucleus

Effect of forced running stress on neuron ultrastructure in the rat arcuate nucleus

The effect of forced running on heat production in brown adipose tissue in rats

The effect of running on heat production in brown adipose tissue (BAT) was compared between trained and untrained rats. Rats were forced to run a treadmill while temperatures of colon (Tcol) and interscapular BAT (Tbat) were measured. The daily running for 5 weeks neither changed the size of interscapular BAT nor the norepinephrine-induced thermogenesis (8 μg/kg·min). During running, both Tbat and Tcol increased. In rats trained for 2 weeks, the increases in Tbat were similar to those in Tcol. In untrained rats, however, the increases in Tbat were larger than those in Tcol. It is suggested that exercise increases heat production in BAT in untrained rats, but such heat production in BAT is abolished by daily exercise. Exercise suppresses cold-induced heat production in BAT of trained rats.

Comparison of the effects of CRF and stress on levels of pituitary cyclic AMP and plasma ACTH in vivo

We have previously reported that acute stress increases levels of rat pituitary cyclic AMP in vivo. The present study was conducted to test the hypothesis that stress-induced increases in pituitary cyclic AMP in vivo were mediated via CRF. We compared the effects of various stressors with the effects of CRF or epinephrine administration on pituitary cyclic AMP and plasma ACTH responses in vivo. Stressors, epinephrine or CRF increased levels of pituitary cyclic AMP. Pituitary cyclic AMP response to either immobilization or CRF was much greater at light onset than at lights off in rats maintained on at 12 hr light: 12 hr dark lighting regimen. In rats with pituitary stalk transections, footshock did not increase levels of pituitary cyclic AMP, suggesting that some factor of central origin was required for this stress response. Exogenous CRF administration did increase levels of pituitary cyclic AMP in stalk-transected rats, while epinephrine increased levels in sham-operated but not in stalk-transected rats. Antisera to CRF markedly decreased pituitary cyclic AMP response to exogenous CRF administered 6 min following antisera and partially attenuated pituitary cyclic AMP response to forced running. Taken as a whole these data support a major role for CRF in the pituitary cyclic AMP response to stress.

THE EFFECT OF EXERCISE AND FASTING ON THE MYOCARDIAL PROTEIN AND LIPID METABOLISM IN EXPERIMENTAL BACTERIAL MYOCARDITIS

A generally nonlethal Salmonella typhimurium infection in weanling rats produced bacterial myocarditis and myocardial hyperplasia. Myocardial lesions were characterized by focal infiltrates of inflammatory cells (predominantly mononuclear), segmental myocyte necrosis, and incipient fibrosis. Although bacterial infections are infrequently associated with myocarditis, the S. typhimurium infection in young rats produced a new experimental model of diffuse myocardial inflammatory foci. Biochemical changes in the myocardium included great increases in total myocardial contents of protein (23%), RNA (39%) and DNA (43%) and several lipid fractions (35-55%) as well as in tissue activities of acid hydrolases, such as cathepsin D (124%) and beta-glucuronidase (135%), all of which contrasted with the relatively limited areas of histologic involvement (1.5%). To study the effects of additional stress in this model infection, some rats were exercised by forced running in wheels for 2 hours and others were fasted for 24 hours before samples were obtained. The short period of forced exercise in this infection caused an additional increase of myocardial protein content (47%) but with no additional change in histology. The expected fasting-induced degradation of protein as well as an infection-associated increase in myocardial lipids were each prevented when rats were fasted during ongoing acute infection. Protein degradation, as reflected by heightened acid hydrolase activities, seemed to occur at a similar rate regardless of other stresses, whereas the rate of myocardial protein synthesis appeared to be alterable.