SEARCH · PubMed Health

Results for “Running”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed2003

Direct effect on validity of response run-in selection in clinical trials.

A run-in is a period prior to randomization during which potential participants who have met all entry criteria for a randomized clinical trial are assigned the same regimen, either the control (possibly placebo) or the experimental treatment. Typically, the intention is to exclude from the subsequent study (i.e., randomization) some segment of this cohort, based on their experiences during the run-in period. Selecting patients based on the run-in thereby forces differential representation of certain subpopulations relative to others. Previous studies have addressed the potential for a run-in to jeopardize validity through unintended mechanisms. While these concerns are valid, they leave open the possibility that modifications to the design of the run-in might be able to preserve validity, even if patient selection is based on the results of the run-in. As such, we address the potential for selecting patients based on response during a run-in period to jeopardize validity directly, through its intended effect of overrepresenting (relative to the screened population) some segments in the randomized portion of the trial and underrepresenting others.

Humans↗

PubMed1997

Outcomes of a placebo run-in period in a head and neck cancer chemoprevention trial.

This study describes the outcomes of an eight-week placebo run-in period in a head and neck cancer chemoprevention trial. Of 391 former cancer patients who entered the run-in over the first two years of the trial, 91% were randomized. Pill counts showed that adherence rates ranged from 0% to 120% (mean 96%, SD = 15%). The trial did not randomize subjects who were no longer interested in trial participation (n = 20), who did not return within 10 weeks of enrollment date (n = 3), or who did not achieve a drug adherence level of at least 75% (n = 9). Three subjects were not randomized for other reasons. Univariate predictors of run-in outcome (randomized or not randomized) included ethnicity, education level, cancer site, cancer stage, and Karnofsky performance score. Multivariate analyses resulted in a logistic model with Karnofsky performance and education level as significant predictors of randomization. Persons with a Karnofsky score of 100 had 2.3 higher odds of randomization (95% CI = 1.1, 4.9) than persons with compromised Karnofsky scores, and persons with more than a high school education had 2.1 higher odds of randomization (95% CI = 1.0, 4.9) than persons with less education. These results suggest that the use of a run-in period may compromise the external validity of randomized prevention trials. More research is needed to understand further the behavioral factors underlying the observed differences so that prevention researchers can develop effective interventions for facilitating trial participation, especially in under-represented, trial-eligible groups. Investigators should expand the objectives of a run-in period to (1) evaluate why eligible persons refuse trial enrollment or fail to be randomized at the end of the run-in and (2) use the run-in period for a systematic evaluation of levels and costs of intervention strategies designed to promote trial enrollment and adherence.

Anticarcinogenic Agents↗

PubMed2001

Was the pedestrian hit in an erect position before being run over?

If a pedestrian was run over by a car, the question can arise whether there was a preceding collision while the pedestrian was in an erect position. From a total of 53 selected autopsy reports, the findings associated with accidents known to involve running over in isolation (n=32) were compared to findings associated with a combined mechanism of a primary impact in an erect position and subsequent running over (n=21). Findings exclusively present in the combined group were wedge-shaped bone fractures ("Messerer"-wedges, 38%), glass fragment injuries (24%), traumatic amputations (10%), traces of car paint on the lower extremities (50%) and abrasions of the shoe soles (17%). These findings can be considered specific for a primary impact in an erect position. Fractures of the cervical and lumbar spine were present in the combined group in 33 and 17%, respectively. In contrast, in the run over group, there was only one case of fracture of the cervical and one of the lumbar spine and both cases involved direct contact with a car wheel. Fractures of the cervical and lumbar spine are, therefore, very indicative for a primary impact. "Bumper injuries", sacroiliac dislocations and fractures of the thoracic spine were approximately 2.5 times more common in the combined group than in the run over group. In the vast majority of cases, a clear differentiation between the two groups is, therefore, possible on the basis of the autopsy findings. This is especially relevant if an inspection of the car cannot be performed after a hit-and-run accident, which occurred in 26% of the cases in this study. In addition, the blood alcohol levels were higher in the run over group (mean=2.14g/l) as compared to the combined group (mean=1.53g/l).

Accidents, Traffic↗

PubMed1998

Time series forecasts of ambulance run volume.

To test the hypothesis that time series analysis can provide accurate predictions of future ambulance service run volume, a prospective stochastic time series modeling study was conducted at a community-based regional ambulance service. For all requests for ambulance transport during two sequential years, the time and date, total run time, and acuity code of the run were recorded in a computer database. Time series variables were formed for ambulance service runs per hour, total run time, and acuity. Prediction models were developed from one complete year's data (1994) and included four model types: raw observations, moving average, means with moving average smoothing, and autoregressive integrated moving average. Forecasts from each model were tested against observations from the first 24 weeks of the subsequent year (1995). Each model's adequacy was tested on residuals by autocorrelation functions, integrated periodograms, linear regression, and differences among the variances. A total of 68,433 patients were seen in 1994 and 32,783 in the first 24 weeks of 1995. Large periodic variations in run volume with time of day were found (P < .001). A model based on arithmetic means of each hour of the week with 3-point moving average smoothing yielded the most accurate forecasts and explained 54.3% of the variation observed in the 1995 test series (P < .001). Time series analysis can provide powerful, accurate short-range forecasts of future ambulance service run volume. Simpler, less expensive models performed best in this study.

Ambulances↗

PubMed2005

Enhanced characterization of complex proteomic samples using LC-MALDI MS/MS: exclusion of redundant peptides from MS/MS analysis in replicate runs.

Due to the complexity of proteome samples, only a portion of peptides and thus proteins can be identified in a single LC-MS/MS analysis in current shotgun proteomics methodologies. It has been shown that replicate runs can be used to improve the comprehensiveness of the proteome analysis; however, high-intensity peptides tend to be analyzed repeatedly in different runs, thus reducing the chance of identifying low-intensity peptides. In contrast to commonly used online ESI-MS, offline MALDI decouples the separation from MS acquisition, thus allowing in-depth selection for specific precursor ions. Accordingly, we extended a strategy for offline LC-MALDI MS/MS analysis using a precursor ion exclusion list consisting of all identified peptides in preceding runs. The exclusion list eliminated redundant MS/MS acquisitions in subsequent runs, thus reducing MALDI sample depletion and allowing identification of a larger number of peptide identifications in the cumulative dataset. In the analysis of the digest of an Escherichia coli lysate, the exclusion list strategy resulted in a 25% increase in the number of unique peptide identifications in the second run, in contrast to simply pooling MS/MS data from two replicate runs. To reduce the increased LC analysis time for repeat runs, a four-column multiplexed LC system was developed to carry out separation simultaneously. The multiplexed LC-MALDI MS provides a high-throughput platform to utilize the exclusion list strategy in proteome analysis.

Amino Acid Sequence↗

PubMed2000

Nesting behavior of house mice (Mus domesticus) selected for increased wheel-running activity.

Nest building was measured in "active" (housed with access to running wheels) and "sedentary" (without wheel access) mice (Mus domesticus) from four replicate lines selected for 10 generations for high voluntary wheel-running behavior, and from four randombred control lines. Based on previous studies of mice bidirectionally selected for thermoregulatory nest building, it was hypothesized that nest building would show a negative correlated response to selection on wheel-running. Such a response could constrain the evolution of high voluntary activity because nesting has also been shown to be positively genetically correlated with successful production of weaned pups. With wheel access, selected mice of both sexes built significantly smaller nests than did control mice. Without wheel access, selected females also built significantly smaller nests than did control females, but only when body mass was excluded from the statistical model, suggesting that body mass mediated this correlated response to selection. Total distance run and mean running speed on wheels was significantly higher in selected mice than in controls, but no differences in amount of time spent running were measured, indicating a complex cause of the response of nesting to selection for voluntary wheel running.

Animals↗

PubMed2003

Involvement of glutamate neurotransmission in the development of excessive wheel running in Lewis rats.

Physical activities such as long-distance running can form a habit and might be related to drug-induced addictive behaviors. We investigated possible modulations of N-methyl-D-aspartate (NMDA) receptor subunits during voluntary wheel running in brain regions implicated in reward and addiction. It was observed that Lewis rats progressively increased their amount of daily running, reaching maximum levels of 4-6 km/day. After 3 weeks of running, mRNA levels coding for NR2A and NR2B subunits were increased in the ventral tegmental area, while only NR2A mRNA levels were found to be elevated in the frontal cortex. Long-term wheel running was also associated with increased binding of specific NMDA receptor antagonist [3H]CGP39653 in the frontal cortex. Moreover, pharmacological inhibition of glutamate release by repeated administration of phenytoin (20 mg/kg IP for 21 days) significantly suppressed daily running. These results suggest that glutamatergic neurotransmission might be related to neurobiological mechanisms underlying the compulsive character of voluntary wheel running.

Animals↗

PubMed2002

1-Methyl-4-phenylpridinium (MPP+)-induced functional run-down of GABA(A) receptor-mediated currents in acutely dissociated dopaminergic neurons.

We have evaluated GABA(A)receptor function during treatment of 1-methyl-4-phenylpridinium (MPP+) using patch-clamp perforated whole-cell recording techniques in acutely dissociated dopaminergic (DAergic) neurons from rat substantia nigra compacta (SNc). Gamma-aminobutyric acid (GABA), glutamate or glycine induced inward currents (I(GABA), I(Glu), I(Gly)) at a holding potential (VH) of -45 mV. The I(GABA) was reversibly blocked by the GABA(A) receptor antagonist, bicuculline, suggesting that I(GABA) is mediated through the activation of GABA(A) receptors. During extracellular perfusion of MPP+ (1-10 microm), I(GABA) , but neither I(Glu) nor I(Gly), declined (termed run-down) with repetitive agonist applications, indicating that the MPP+-induced I(GABA) run-down occurred earlier than I(Gly) or I(Glu) under our experimental conditions. The MPP+-induced I(GABA) run-down can be prevented by a DA transporter inhibitor, mazindol, and can be mimicked by a metabolic inhibitor, rotenone. Using conventional whole-cell recording with different concentrations of ATP in the pipette solution, I(GABA) run-down can be induced by decreasing intracellular ATP concentrations, or prevented by supplying intracellular ATP, indicating that I(GABA) run-down is dependent on intracellular ATP concentrations. A GABA(A) receptor positive modulator, pentobarbital (PB), potentiated the declined I(GABA) and eliminated I(GABA) run-down. Corresponding to these patch-clamp data, tyrosine hydroxylase (TH) immunohistochemical staining showed that TH-positive cell loss was protected by PB during MPP+ perfusion. It is concluded that extracellular perfusion of MPP+ induces a functional run-down of GABA(A) receptors, which may cause an imbalance of excitation and inhibition of DAergic neurons.

1-Methyl-4-phenylpyridinium↗

PubMed2001

The enhanced effect of a hexameric deoxyriboguanosine run conjugation to CpG oligodeoxynucleotides on protection against allergic asthma.

BACKGROUND: Oligodeoxynucleotides containing a CpG motif (CpG ODNs), as potent inducers of T(H)1 immunity, are considered promising candidates for immune modulation in asthma. We have previously demonstrated that conjugation of a hexameric deoxyriboguanosine run to the 3' terminus (3' dG(6)-run) of phosphodiester (PE) CpG ODNs enhanced their immuno-stimulatory activities in vitro. OBJECTIVE: This study aimed to evaluate the effect of a 3' dG(6)-run conjugation to PE or phosphorothioate (PS) CpG ODNs on protection against murine allergic asthma in vivo. METHODS: Balb/c mice were sensitized to ovalbumin by intraperitoneal injection with or without CpG ODNs (PS CpG ODNs, PE CpG ODNs, and those with 3' dG(6)-run) and subsequently challenged with ovalbumin. We evaluated airway hyperresponsiveness, eosinophil proportion in bronchoalveolar lavage fluid, airway inflammation, and ovalbumin-specific antibody responses. RESULTS: The conjugation of a 3' dG(6)-run to PE CpG ODNs enhanced the production of IFN-gamma from ovalbumin-specific T(H) cells and prevented the development of asthma in terms of airway hyperresponsiveness, airway eosinophilia, and ovalbumin-specific IgE responses; these effects were comparable to those of PS CpG ODNs. Enhanced effects of the 3' dG(6)-run were also observed in PS CpG ODNs, though they were lower than those in PE CpG ODNs. CONCLUSION: This study suggests that conjugation of a 3' dG(6)-run to CpG ODNs might provide an effective method for immune modulation of allergic asthma.

Animals↗

PubMed2002

Walking and running at resonance.

Humans and other animals can temporarily store mechanical energy in elastic oscillations, f(el), of body parts and in pendulum oscillations, f(p) = const sq.rt (g/L), of legs, length L, or other appendages, and thereby reduce the energy consumption of locomotion. However, energy saving only occurs if these oscillations are tuned to the leg propagation frequency f. It has long been known that f is tuned to the pendulum frequency of the free-swinging leg of walkers. During running the leg frequency increases to some new value f = f(r). We propose that in order to maintain resonance the animal, mass M, actively increases its leg pendulum frequency to the new value f(p,r) =const sq.rt (a(y)/L)=f(r), by giving its hips a vertical acceleration a(y)= F(y)/M. The pendulum frequency is increased if the impact force F(y) of the stance foot is larger than Mg, explaining the observation by Alexander and Bennet-Clark (1976) that F(v) becomes larger than Mg when animals start to run. Our model predictions of the running velocity U(r) as function of L, F(v), are in agreement with measurements of these quantities (Farley et al. 1993). The leg's longitudinal elastic oscillation frequency scales as f(el) = const sq.rt (k/M). Experiments by Ferris et al., (1998) show that runners adjust their leg's stiffness, k, when running on surfaces of different elasticity so that the total stiffness k remains constant. Our analysis of their data suggests that the longitudinal oscillations of the stance leg are indeed kept in tune with the running frequency. Therefore we conclude that humans, and by extension all animals, maintain resonance during running. Our model also predicts the Froude number of walking-running transitions, Fr = U(2)/gL approximately 0.5 in good agreement with measurements.

Journal Article↗

PubMed2002

Preference for a solution of branched-chain amino acids plus glutamine and arginine correlates with free running activity in rats: involvement of serotonergic-dependent processes of lateral hypothalamus.

Rats were given free access to a running wheel, food, water, and a solution composed of branched-chain amino acids plus glutamine and arginine (the "BCAA-based" solution). A positive relationship between dark-period running distance and preference for the BCAA-based solution was observed. Serotonin release in the lateral hypothalamus, the central nucleus of amygdala and the medial nucleus raphe in overnight fluid-deprived rats during their first subsequent free drinking was also measured. A lowered serotonin release in the lateral hypothalamus characterized the rats that consumed the BCAA-based solution. No drink-related changes were observed in the amygdala. A separate group of rats was trained on a treadmill. Following the training period, plasma amino acids and brain serotonin release were measured during running. The BCAA-based solution infused before running elevated the branched chain amino acids/tryptophan plasma ratio at the end of, and after, running. Additionally, a decreased lateral hypothalamus serotonin release was seen 80 min after running, when compared with water-infused rats. No fluid-related changes in the amygdala were observed. The exercise-related shift in the fluid preference towards a BCAA-based solution suggests an ergogenic benefit. The forced-running study shows the lateral hypothalamus as a critical region in the effects of a BCAA-based solution.

Amino Acids, Branched-Chain↗

PubMedDate not supplied

Energy cost of wheel running in house mice: implications for coadaptation of locomotion and energy budgets.

Laboratory house mice (Mus domesticus) that had experienced 10 generations of artificial selection for high levels of voluntary wheel running ran about 70% more total revolutions per day than did mice from random-bred control lines. The difference resulted primarily from increased average velocities rather than from increased time spent running. Within all eight lines (four selected, four control), females ran more than males. Average daily running distances ranged from 4.4 km in control males to 11.6 km in selected females. Whole-animal food consumption was statistically indistinguishable in the selected and control lines. However, mice from selected lines averaged approximately 10% smaller in body mass, and mass-adjusted food consumption was 4% higher in selected lines than in controls. The incremental cost of locomotion (grams food/revolution), computed as the partial regression slope of food consumption on revolutions run per day, did not differ between selected and control mice. On a 24-h basis, the total incremental cost of running (covering a distance) amounted to only 4.4% of food consumption in the control lines and 7.5% in the selected ones. However, the daily incremental cost of time active is higher (15.4% and 13.1% of total food consumption in selected and control lines, respectively). If wheel running in the selected lines continues to increase mainly by increases in velocity, then constraints related to energy acquisition are unlikely to be an important factor limiting further selective gain. More generally, our results suggest that, in small mammals, a substantial evolutionary increase in daily movement distances can be achieved by increasing running speed, without remarkable increases in total energy expenditure.

Adaptation, Physiological↗

PubMed2005

Voluntary wheel running improves recovery from a moderate spinal cord injury.

Recently, locomotor training has been shown to improve overground locomotion in patients with spinal cord injury (SCI). This has triggered renewed interest in the role of exercise in rehabilitation after SCI. However, there are no mouse models for voluntary exercise and recovery of function following SCI. Here, we report voluntary wheel running improves recovery from a SCI in mice. C57Bl/10 female mice received a 60-kdyne T9 contusion injury with an IH impactor after 3 weeks of voluntary wheel running or 3 weeks of standard single housing conditions. Following a 7-day recovery period, running mice were returned to their running wheels. Weekly open-field behavior measured locomotor recovery using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale and the Basso Mouse Scale (BMS) locomotor rating scale, a scale recently developed specifically for mice. Initial experiments using standard rung wheels show that wheel running impaired recovery, but subsequent experiments using a modified flat-surface wheel show improved recovery with exercise. By 14 days post SCI, the modified flat-surface running group had significantly higher BBB and BMS scores than the sedentary group. A repeated measures ANOVA shows locomotor recovery of modified flat-surface running mice was significantly improved compared to sedentary animals (p < 0.05). Locomotor assessment using a ladder beam task also shows a significant improvement in the modified flat-surface runners (p < 0.05). Finally, fibronectin staining shows no significant difference in lesion size between the two groups. These data represent the first mouse model showing voluntary exercise improves recovery after SCI.

Animals↗

PubMed2000

Molecular determinant for run-down of L-type Ca2+ channels localized in the carboxyl terminus of the 1C subunit.

1. The role of the sequence 1572-1651 in the C-terminal tail of the alpha1C subunit in run-down of Ca2+ channels was studied by comparing functional properties of the conventional alpha1C,77 channel with those of three isoforms carrying alterations in this motif. 2. The pore-forming alpha1C subunits were co-expressed with alpha2delta and beta2a subunits in HEK-tsA201 cells, a subclone of the human embryonic kidney cell line, and studied by whole-cell and single-channel patch-clamp techniques. 3. Replacement of amino acids 1572-1651 in alpha1C,77 with 81 different amino acids leading to alpha1C,86 significantly altered run-down behaviour. Run-down of Ba2+ currents was rapid with alpha1C,77 channels, but was slow with alpha1C,86. 4. Transfer of the alpha1C,86 segments L (amino acids 1572-1598) or K (amino acids 1595-1652) into the alpha1C,77 channel yielded alpha1C,77L and alpha1C,77K channels, respectively, the run-down of which resembled more that of alpha1C,77. These results demonstrate that a large stretch of sequence between residues 1572 and 1652 of alpha1C,86 renders Ca2+ channels markedly resistant to run-down. 5. The protease inhibitor calpastatin added together with ATP was able to reverse the run-down of alpha1C,77 channels. Calpastatin expression was demonstrated in the HEK-tsA cells by Western blot analysis. 6. These results indicate a significant role of the C-terminal sequence 1572-1651 of the alpha1C subunit in run-down of L-type Ca2+ channels and suggest this sequence as a target site for a modulatory effect by endogenous calpastatin.

Amino Acid Sequence↗

PubMed1991

Run-down of neuromuscular transmission during repetitive nerve activity by nicotinic antagonists is not due to desensitization of the postsynaptic receptor.

1. Whether the function of the postsynaptic acetylcholine receptor is use-dependently affected by repetitive nerve stimulation in the presence of competitive antagonists was studied in the mouse phrenic nerve-hemidiaphragm preparation. 2. For electrophysiological experiments, the preparation was immobilized by synthetic mu-conotoxin, which preferentially blocks muscular Na-channels causing neither depolarization of the membrane potential, inhibition of quantal transmitter release, nor depression of nicotinic receptor function. 3. High concentrations of cobratoxin depressed indirect twitches and endplate potentials (e.p.ps) without inducing waning of contractilities or run-down of trains of e.p.ps evoked at 10-100 Hz. However, waning and run-down were accelerated after washout of the toxin despite diminished postsynaptic receptor blockade. Once the run-down of e.p.ps was produced by washout or low concentrations of cobratoxin, further depression of e.p.p. amplitude with high concentrations of cobratoxin did not attenuate the e.p.p. run-down. 4. The degrees of waning of tetanus and trains of e.p.ps produced by a very high concentration of tubocurarine (20 microM) were also less than that caused at a 100 fold lower concentration, albeit the amplitudes of twitches and the first e.p.p. were depressed more rapidly and markedly. 5. Tubocurarine, like cobratoxin, depressed the amplitude of miniature endplate potentials (m.e.p.ps) more than e.p.ps. 6. In contrast to the steepened run-down of successive e.p.ps in the presence of low concentrations of either nicotinic antagonists, the amplitude of m.e.p.ps observed during repetitive stimulation was uniform and was not different from that before stimulation. 7. The results suggest that the e.p.p. run-down and tetanic fade induced by nicotinic antagonists are due to a slow kinetic blockade of presynaptic receptors and confirm that the e.p.p. run-down is not produced by a use-dependent failure of postsynaptic nicotinic receptors. The roles of the presynaptic nicotinic receptor in positive or negative feedback modulations of transmitter release are discussed.

Acetylcholine↗

PubMed1997

Hypermutability of homonucleotide runs in mismatch repair and DNA polymerase proofreading yeast mutants.

Homonucleotide runs in coding sequences are hot spots for frameshift mutations and potential sources of genetic changes leading to cancer in humans having a mismatch repair defect. We examined frameshift mutations in homonucleotide runs of deoxyadenosines ranging from 4 to 14 bases at the same position in the LYS2 gene of the yeast Saccharomyces cerevisiae. In the msh2 mismatch repair mutant, runs of 9 to 14 deoxyadenosines are 1,700-fold to 51,000-fold, respectively, more mutable for single-nucleotide deletions than are runs of 4 deoxyadenosines. These frameshift mutations can account for up to 99% of all forward mutations inactivating the 4-kb LYS2 gene. Based on results with single and double mutations of the POL2 and MSH2 genes, both DNA polymerase epsilon proofreading and mismatch repair are efficient for short runs while only the mismatch repair system prevents frameshift mutations in runs of > or = 8 nucleotides. Therefore, coding sequences containing long homonucleotide runs are likely to be at risk for mutational inactivation in cells lacking mismatch repair capability.

Base Sequence↗

PubMedDate not supplied

Predicting submaximal oxygen consumption during treadmill running in mice.

Treadmill exercise is the most common form of exercise used in studies involving laboratory rodents. However, oxygen consumption (VO2) is not usually monitored since the measurement of this parameter is particularly difficult in small, exercising animals. The purpose of this study was to develop a regression equation for predicting submaximal VO2 in mice during treadmill running. Twenty female mice of three strains were tested, in an Oxyscan metabolic treadmill, on different days at running speeds of 10, 13, 15, 17, and 20 m/min at a 0% grade. Each mouse was placed in the treadmill chamber for a 10-min period before running commenced. Running speed was increased in 2-min intervals by 5 m/min until the assigned speed was reached. Each mouse then ran for 10 min to reach steady state, followed by another 20 min at the steady-state plateau. During this period a 30-s expired gas sample was collected every minute. Gas samples were analyzed for O2 and CO2, using an Oxyscan gas analyzer. Trials were conducted during the nocturnal phase of the animals' photoperiod, and running speeds were assigned randomly to minimize order effects. This approach provided highly reliable measures of oxygen consumption (r = 0.96). By using the running speeds (10-20 m/min) and the animal's body weight it was possible to predict the submaximal oxygen consumption (mL/min) during running with a high degree of accuracy (i.e., R2 = 0.85). In an independent group of animals (n = 14) we compared the predicted VO2 with the measured VO2. This yielded a good correlation coefficient (r = 0.79) and a low prediction error (+2.4 +/- 2.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Diurnal variation of intensive running in food-deprived rats.

Manipulation of the food supply can induce either intense hyperactive wheel running or a fatal activity anorexia in rats that is strongly analogous to that seen in humans. The abnormal behaviour is accompanied by alterations in the diurnal pattern of activity. As part of a detailed study of hyperactivity and anorexia, spontaneous wheel running by male rats was studied under three conditions: ad libitum feeding; restriction to 15 g of food per day; and restriction to a single 90-min meal per day. Ad libitum fed rats increased their running at the rate of 440 +/- 60 m/day per day, stabilizing after day 10 at 6045 +/- 3010 m/day. The running occurred in short bursts throughout the dark period and at the beginning of the light period. Rats restricted to 15 g/day increased their running at the significantly greater (p < 0.001) rate of 1230 +/- 120 m/day per day, reaching 12 200 +/- 4 090 m/day by day 10 and thereafter stabilizing at 13 600 +/- 4 160 m/day. The running was initially triphasic and confined to the dark period but eventually progressed to a biphasic pattern. The rats restricted to a single 90-min access period to food each day showed an even greater rate of increase in running, attaining 1930 +/- 288 m/day per day (p < 0.02 vs. 15 g/day group). These animals decreased eating and decompensated by day 4. The diurnal pattern of activity was disturbed from day 1 of the protocol, and by day 4 the rats ran essentially continuously throughout the daily cycle. The sensitivity to hyperactivity is a function of the severity of food restriction in this animal model of hyperactivity. It is paralleled by a marked disturbance of the diurnal pattern of activity, suggesting that the hyperactivity is related to a basic central nervous system dysfunction.

Animals↗