Access To Wheel Research Articles

Acute Restraint Stress Alters Wheel-Running Behavior Immediately Following Stress and up to 20 Hours Later in House Mice.

In vertebrates, acute stressors-although short in duration-can influence physiology and behavior over a longer time course, which might have important ramifications under natural conditions. In laboratory rats, for example, acute stress has been shown to increase anxiogenic behaviors for days after a stressor. In this study, we quantified voluntary wheel-running behavior for 22 h following a restraint stress and glucocorticoid levels 24 h postrestraint. We utilized mice from four replicate lines that have been selectively bred for high voluntary wheel-running activity (HR mice) for 60 generations and their nonselected control (C) lines to examine potential interactions between exercise propensity and sensitivity to stress. Following 6 d of wheel access on a 12L∶12D photo cycle (0700-1900 hours, as during the routine selective breeding protocol), 80 mice were physically restrained for 40 min, beginning at 1400 hours, while another 80 were left undisturbed. Relative to unrestrained mice, wheel running increased for both HR and C mice during the first hour postrestraint (P < 0.0001) but did not differ 2 or 3 h postrestraint. Wheel running was also examined at four distinct phases of the photoperiod. Running in the period of 1600-1840 hours was unaffected by restraint stress and did not differ statistically between HR and C mice. During the period of peak wheel running (1920-0140 hours), restrained mice tended to run fewer revolutions (-11%; two-tailed P = 0.0733), while HR mice ran 473% more than C (P = 0.0008), with no restraint × line type interaction. Wheel running declined for all mice in the latter part of the scotophase (0140-0600 hours), restraint had no statistical effect on wheel running, but HR again ran more than C (+467%; P = 0.0122). Finally, during the start of the photophase (0720-1200 hours), restraint increased running by an average of 53% (P = 0.0443) in both line types, but HR and C mice did not differ statistically. Mice from HR lines had statistically higher plasma corticosterone concentrations than C mice, with no statistical effect of restraint and no interaction between line type and restraint. Overall, these results indicate that acute stress can affect locomotor activity (or activity patterns) for many hours, with the most prominent effect being an increase in activity during a period of typical inactivity at the start of the photophase, 15-20 h poststressor.

Effect of High Fat/High Sugar Diet &amp; Physical Activity on Sex Hormone Concentrations

BACKGROUND: Physical inactivity in combination with poor nutrition promotes obesity and is the second leading cause of death in the US. It is well known that physical activity (PA) mitigates the incidence of obesity related diseases. Yet, most individuals fail to meet daily recommended PA requirements. Available animal literature suggests that one primary factor that regulates PA is sex hormones. PURPOSE: This study examined the effects of a high fat/high sugar (HF/HS) diet on Testosterone (T) and 17β-Estradiol (E2) concentrations in female mice with and without physical activity. METHODS: All procedures were approved by TAMU IACUC. The offspring of SENCAR breeder pairs (Charles River) were weaned and co-caged at three weeks of age and randomly assigned to a HF/HS diet (45% fat/10% fructose drinking water) (n=6) or ad-lib (AL) control diet (10% fat) (n=4). At four weeks of age, mice were provided with running wheel access. Running speed, distance, and duration were recorded daily until termination at 20wks of age. Serum T and E2 concentrations were analyzed via ELISA. A 2-way ANOVA was utilized to assess significant differences. RESULTS: E2 concentrations in the AL fed mice with- and without-PA (0.30±0.03; 0.26±0.03 ng/ml) and in the HF/HS fed mice with- and without-PA (0.28±0.04; 0.27±0.23 ng/ml), were not affected by diet type, but were significantly affected by PA (p=0.03). T concentrations in the AL fed mice with- and without-PA (0.33±0.01; 0.31±0.34 ng/ml) and in the HF/HS fed mice with- and without-PA (0.46±0.22; 0.21±0.14 ng/ml) demonstrated no significant effect of diet or PA. CONCLUSION: In this study neither T nor E2 concentrations were altered by HF/HS diet. However, PA increased the serum concentrations of E2, but not T. Therefore, physical activity can affect estradiol levels independent of diet. ACKNOWLEDGMENTS: This project was funded by the US Army through the Department of Defense projects W81XWH-13-1-0278 (Fuchs-Young) and W81XWH-13-1-0279 (Lightfoot).

Cerebellar sub-divisions differ in exercise-induced plasticity of noradrenergic axons and in their association with resilience to activity-based anorexia

The vermis or “spinocerebellum” receives input from the spinal cord and motor cortex for controlling balance and locomotion, while the longitudinal hemisphere region or “cerebro-cerebellum” is interconnected with non-motor cortical regions, including the prefrontal cortex that underlies decision-making. Noradrenaline release in the cerebellum is known to be important for motor plasticity but less is known about plasticity of the cerebellar noradrenergic (NA) system, itself. We characterized plasticity of dopamine β-hydroxylase-immunoreactive NA fibers in the cerebellum of adolescent female rats that are evoked by voluntary wheel running, food restriction (FR) or by both, in combination. When 8 days of wheel access was combined with FR during the last 4 days, some responded with excessive exercise, choosing to run even during the hours of food access: this exacerbated weight loss beyond that due to FR alone. In the vermis, exercise, with or without FR, shortened the inter-varicosity intervals and increased varicosity density along NA fibers, while excessive exercise, due to FR, also shortened NA fibers. In contrast, the hemisphere required the FR-evoked excessive exercise to evoke shortened inter-varicosity intervals along NA fibers and this change was exhibited more strongly by rats that suppressed the FR-evoked excessive exercise, a behavior that minimized weight loss. Presuming that shortened inter-varicosity intervals translate to enhanced NA release and synthesis of norepinephrine, this enhancement in the cerebellar hemisphere may contribute towards protection of individuals from the life-threatening activity-based anorexia via relays with higher-order cortical areas that mediate the animal’s decision to suppress the innate FR-evoked hyperactivity.

Effects of HMB and beta‐alanine co‐supplementation and running wheel activity on skeletal muscle morphometry and metabolomics in aged rats

Dietary intervention with either beta‐hydroxy‐beta‐methylbutyrate (HMB) or beta‐alanine (BA) has been shown to improve muscle strength and physical working capacity, respectively, in elderly subjects. We examined the effects of 8 weeks HMB (343 mg/kg bw) and BA (274 mg/kg bw) co‐supplementation (HMB+BA) on skeletal muscle morphometry and metabolomic profiles in aged, male Sprague Dawley rats (22 months), versus AIN‐93M control diet (CTL). Rats were also assigned either continuous voluntary running wheel access (RW+) or cage‐matched without running wheel access (RW‐). Thus, we examined a total of 4 experimental groups (9–10 rats per group). RW activity across the 8 weeks of study was very low across both diet groups, and the HMB+BA diet had no significant effect on RW activity compared to rats fed CTL diet (84 ± 17 m/day vs. 73 ± 16 m/day). The HMB+BA diet also had no significant effects on food intake or body weight in either RW‐ or RW+ rats. Across both RW+ groups, average % body weight change decreased compared to the RW‐ groups (0.2% vs. 6.1%, P&lt;0.00001). RW activity also decreased average weekly food intake by 6.1% (125 ± 2 g vs. 133 ± 2 g, P=0.023). Neither HMB+BA supplementation nor RW activity had significant effects on forelimb grip strength or absolute hindlimb muscle weights (i.e., gastrocnemius, soleus, plantaris). HMB+BA/RW‐ rats showed a trend for increased gastrocnemius myofiber cross‐sectional area (3430 ± 134 μm2 vs. 3802 ± 152 μm2, P=0.084), however with minimal effect on myofiber Feret diameter, relative to CTL/RW‐ rats. Metabolomic profiling highlighted effects of RW activity and HMB+BA diet on carbohydrate and lipid metabolism. In gastrocnemius, RW activity was associated with a decrease in the glycolytic intermediate, fructose‐6‐phosphate, and this effect was more pronounced in combination with the HMB+BA diet. The HMB+BA/RW+ group also showed a significant reduction in pyruvate and citrate, relative to all other groups. Adenine and 2′‐ deoxycytidine levels were also less abundant with the HMB+BA diet. Metabolomic profiling was also carried out on rectus femoris muscle from the RW‐ groups only, and the HMB+BA diet was associated with increased long chain fatty acids (LCFAs), relative to CTL diet. Increased LCFAs may indicate enhanced beta‐oxidation of lipids, and the aforementioned decreases in glycolytic intermediates suggest improved carbohydrate metabolism, as we have previously shown that these biochemicals are more abundant with age in muscle. Altogether, these data suggest that both low‐volume physical activity and HMB+BA co‐supplementation contribute to improved bioenergetics in aging skeletal muscle.Support or Funding InformationFunding for this study was provided by Abbott Nutrition.

Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference.

Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference.

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex ‘omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10–11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

Endocannabinoids mediate runner’s high

Endocannabinoids, rather than endorphins, mediate some of the feelings associated with “runner’s high.”

Comparative adaptations in oxidative and glycolytic muscle fibers in a low voluntary wheel running rat model performing three levels of physical activity

A unique polygenic model of rat physical activity has been recently developed where rats were selected for the trait of low voluntary wheel running. We utilized this model to identify differences in soleus and plantaris muscles of sedentary low voluntary wheel running rats and physically active low voluntary wheel running rats exposed to moderate amounts of treadmill training. Three groups of 28-day-old male Wistar rats were used: (1) rats without a running wheel (SEDENTARY, n = 7), (2) rats housed with a running wheel (WHEEL, n = 7), and (3) rats housed with a running wheel and exercised on the treadmill (5 days/week for 20 min/day at 15.0 m/min) (WHEEL + TREADMILL, n = 7). Animals were euthanized 5 weeks after the start of the experiment and the soleus and plantaris muscles were excised and used for analyses. Increases in skeletal muscle gene expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and fibronectin type III domain-containing protein 5 in WHEEL + TREADMILL group were observed. Also, WHEEL + TREADMILL had higher protein levels of superoxide dismutase 2 and decreased levels of oxidative damage. Our data demonstrate that the addition of treadmill training induces beneficial muscular adaptations compared to animals with wheel access alone. Furthermore, our data expand our understanding of differential muscular adaptations in response to exercise in mitochondrial, antioxidant, and metabolic markers.

Reduced metabolic disease risk profile by voluntary wheel running accompanying juvenile Western diet in rats bred for high and low voluntary exercise

Metabolic disease risk is influenced by genetics and modifiable factors, such as physical activity and diet. Beginning at 6weeks of age, rats selectively bred for high (HVR) versus low voluntary running distance (LVR) behaviors were housed in a complex design with or without voluntary running wheels being fed either a standard or Western (WD, 42% kcal from fat and added sucrose) diet for 8 weeks. Upon intervention completion, percent body fat, leptin, insulin, and mediobasal hypothalamic mRNAs related to appetite control were assessed. Wheel access led to differences in body weight, food intake, and serum leptin and insulin. Intriguingly, percent body fat, leptin, and insulin did not differ between HVR and LVR lines in response to the two levels of voluntary running, regardless of diet, after the 8wk. experiment despite HVR eating more calories than LVR regardless of diet and voluntarily running 5–7 times further in wheels than LVR. In response to WD, we observed increases in Cart and Lepr mediobasal hypothalamic mRNA in HVR, but no differences in LVR. Npy mRNA was intrinsically greater in LVR than HVR, while wheel access led to greater Pomc and Cart mRNA in LVR versus HVR. These data suggest that despite greater consumption of WD, HVR animals respond similarly to WD as LVR as a result, in part, of their increased wheel running behavior. Furthermore, high physical activity in HVR may offset the deleterious effects of a WD on adiposity despite greater energy intake in this group.

Exercise alters the gut microbiome and microbial metabolites: Implications for colorectal cancer and inflammatory bowel disease

Introduction Exercise training reduces colon cancer and inflammatory bowel diseases (IBD), but the mechanisms remain unknown. We hypothesized that acute and chronic exercise would alter the gut microbiota and its associated metabolome in a beneficial way. Methods Mice exercised for 6 weeks with access to voluntary wheels (VWR; n = 10), or were forcibly run on a treadmill running (FTR; n = 10). A control group remained sedentary (SED; n = 9). The conserved bacterial 16s rRNA gene was isolated from the feces and cecum and sequenced using high-throughput Illumina Miseq. In another experiment, mice were randomized to sedentary (SED, n = 10), acute moderate (MOD, n = 10) or high intensity running (HI, n = 10). Mice were euthanized 45 min post and cecal contents were analyzed for short chain fatty acids (SCFA) by GC-MS. Results Exercise training differentially altered the community structure of the microbiome at both intestinal sites ( p 0.05 ). Further evaluation revealed that exercise altered many bacterial taxa in both the feces and the cecum. Notably, voluntary exercise reduced ceca and fecal concentrations of Turicibacter spp., a genus of bacteria implicated in ulcerative colitis in humans and mice. Acute, HI (but not MOD) exercise increased the levels of potentially beneficial acetate, propionate, and butyrate, compared to SED ( p 0.05 ). Conclusion Acute and chronic exercise invokes changes in the microbiome and metabolome that may be beneficial to the prevention or treatment of IBD and colon cancer.

Developmental effects of wheel running on hippocampal glutamate receptor expression in young and mature adult rats

Recent evidence suggests that the behavioral benefits associated with voluntary wheel running in rodents may be due to modulation of glutamatergic transmission in the hippocampus, a brain region implicated in learning and memory. However, the expression of the glutamatergic ionotropic N-methyl-d-aspartate receptor (GluN) in the hippocampus in response to chronic sustained voluntary wheel running has not yet been investigated. Further, the developmental effects during young and mature adulthood on wheel running output and GluN expression in hippocampal subregions has not been determined, and therefore is the main focus of this investigation. Eight-week-old and 16-week-old male Wistar rats were housed in home cages with free access to running wheels and running output was monitored for 4weeks. Wheel access was terminated and tissues from the dorsal and ventral hippocampi were processed for Western blot analysis of GluN subunit expression. Young adult runners demonstrated an escalation in running output but this behavior was not evident in mature adult runners. In parallel, young adult runners demonstrated a significant increase in total GluN (1 and 2A) subunit expression in the dorsal hippocampus (DH), and an opposing effect in the ventral hippocampus (VH) compared to age-matched sedentary controls; these changes in total protein expression were not associated with significant alterations in the phosphorylation of the GluN subunits. In contrast, mature adult runners demonstrated a reduction in total GluN2A expression in the DH, without producing alterations in the VH compared to age-matched sedentary controls. In conclusion, differential running activity-mediated modulation of GluN subunit expression in the hippocampal subregions was revealed to be associated with developmental effects on running activity, which may contribute to altered hippocampal synaptic activity and behavioral outcomes in young and mature adult subjects.

Effects of early-onset voluntary exercise on adult physical activity and associated phenotypes in mice

The purpose of this study was to evaluate the effects of early-life exercise on adult physical activity (wheel running, home-cage activity), body mass, food consumption, and circulating leptin levels in males from four replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR) and their four non-selected control (C) lines. Half of the mice were given wheel access shortly after weaning for three consecutive weeks. Wheel access was then removed for 52 days, followed by two weeks of adult wheel access for all mice. A blood sample taken prior to adult wheel testing was analyzed for circulating leptin concentration. Early-life wheel access significantly increased adult voluntary exercise on wheels during the first week of the second period of wheel access, for both HR and C mice, and HR ran more than C mice. During this same time period, activity in the home cages was not affected by early-age wheel access, and did not differ statistically between HR and C mice. Throughout the study, all mice with early wheel access had lower body masses than their sedentary counterparts, and HR mice had lower body masses than C mice. With wheel access, HR mice also ate significantly more than C mice. Early-life wheel access increased plasma leptin levels (adjusted statistically for fat-pad mass as a covariate) in C mice, but decreased them in HR mice. At sacrifice, early-life exercise had no statistically significant effects on visceral fat pad, heart (ventricle), liver or spleen masses (all adjusted statistically for variation in body mass). Results support the hypothesis that early-age exercise in mice can have at least transitory positive effects on adult levels of voluntary exercise, in addition to reducing body mass, and may be relevant for the public policy debates concerning the importance of physical education for children.

Effects of voluntary exercise on spontaneous physical activity and food consumption in mice: Results from an artificial selection experiment

We evaluated the effect of voluntary exercise on spontaneous physical activity (SPA) and food consumption in mice from 4 replicate lines bred for 57 generations for high voluntary wheel running (HR) and from 4 non-selected control (C) lines. Beginning at ~24days of age, mice were housed in standard cages or in cages with attached wheels. Wheel activity and SPA were monitored in 1-min intervals. Data from the 8th week of the experiment were analyzed because mice were sexually mature and had plateaued in body mass, weekly wheel running distance, SPA, and food consumption. Body mass, length, and masses of the retroperitoneal fat pad, liver, and heart were recorded after the 13th week. SPA of both HR and C mice decreased with wheel access, due to reductions in both duration and average intensity of SPA. However, total activity duration (SPA+wheel running; min/day) was ~1/3 greater when mice were housed with wheels, and food consumption was significantly increased. Overall, food consumption in both HR and C mice was more strongly affected by wheel running than by SPA. Duration of wheel running had a stronger effect than average speed, but the opposite was true for SPA. With body mass as a covariate, chronic wheel access significantly reduced fat pad mass and increased heart mass in both HR and C mice. Given that both HR and C mice housed with wheels had increased food consumption, the energetic cost of wheel running was not fully compensated by concomitant reductions in SPA. The experiment demonstrates that both duration and intensity of both wheel running and SPA were significant predictors of food consumption. This sort of detailed analysis of the effects of different aspects of physical activity on food consumption has not previously been reported for a non-human animal, and it sets the stage for longitudinal examination of energy balance and its components in rodent models.

Exercise reward induces appetitive 50-kHz calls in rats

Rats express affective states by visible behaviors (like approach or flight) and through different kinds of ultrasonic vocalizations (USV). 50-kHz calls are thought to reflect positive affective states since they occur during rewarding situations like social play or palatable food. However, the effects of voluntary exercise on USV have not been investigated yet, although such exercise can serve as reward. To this aim, we gave young adult rats restricted daily access to a runway maze, where they could interact with either a movable (experimental group) or locked wheel (sedentary group) for 14days and we tested USV in anticipation of and during subsequent running. We also studied inter-individual differences in running, and relationships with USV, and rat-typical trait measures. The results showed that the experimental rats had to be separated into “runners” and “pseudorunners” since only runners performed true running, whereas pseudorunners hardly entered the wheel and turned it only with their forelimbs. This outcome seems to be related to subject-dependent differences in responding to novelty and in reward sensitivity, as indicated by pertinent screening tests, which we had performed prior to the 14days of wheel access. In the runway, our experimental and control groups did not differ in visible anticipatory behavior, like approach. Yet, only runners and sedentary rats displayed an increasing but similar amount of anticipatory USV, which is suggestive of a state of incentive anticipation of the coming wheel access. During exercise, only runners increased USV, probably indicating a highly positive emotional state. To conclude, voluntary exercise provides a promising tool to induce 50-kHz USV during and in anticipation of exercise. When performing such studies, possible individual differences between subjects have to be taken into account, and the actual wheel performance should carefully be controlled.

The role of skeletal muscle characteristics in the decline of VO2peak in rats

Maximal aerobic capacity is a strong predictor or mortality in humans and rodents. It has been established that VO2peak declines with age beginning in the 3rd decade of life in humans. There is a paucity of data examining the underlying mechanisms that may be responsible for this VO2peak decline. Organ systems that likely play significant roles include the heart, brain and skeletal muscle. The purpose of this study was to assess skeletal muscles role during the initial decline from lifetime apex‐VO2peak in rats, and to assess the ability of physical activity to modify the decline. Two groups of rats, one with access to a voluntary running wheel (WG) and one with no wheel access (NWG) underwent VO2peak testing weekly beginning at 10 weeks of age until the end of the study. Voluntary wheel running began at 5‐weeks of age and peaked at 10‐weeks of age. Lifetime apex‐VO2peak occurred at 19 weeks of age, and decreased until reaching a steady at 27 weeks of age. There was no difference in mass between 19‐weeks and 27‐weeks in tricep, gastrocnemius, and soleus muscles, discounting the previous associations between declining muscle mass and VO2peak. Currently, we are deciding which of these muscles to use for subsequent analysis. To this end, PGC1α mRNA was compared in all three muscles between 19 and 27‐weeks to aid in selecting a muscle for RNA‐sequencing and protein analysis. PGC1α mRNA was not different in any muscle between 19 and 27‐weeks of age. PGC1α in the tricep showed the WG had 150% higher expression at both 19 and 27 weeks of age compared to the NWG. Also, mitochondrial quantity is being assessed through protein analysis of COX‐IV and cytochrome c. This will aid in our decision for selection of one skeletal muscle to perform RNA‐sequencing on.

Exercise Attenuates Age‐Associated Reductions in Muscle Strength and Cardiorespiratory Fitness in Mice

Aging is associated with losses in muscle strength and cardiovascular fitness that may be offset with regular exercise. While exercise adaptations may diminish with age, robust adaptations still occur. We tested the hypothesis that aging reduces muscle function and cardiorespiratory endurance, however voluntary (running wheel, RW) or prescribed (treadmill (TM) training) exercise will attenuate these aging‐associated decreases in strength and fitness. In vivo plantarflexor maximal force and fatigue (% of max force after 10 contractions) were measured in young (4 mo. old) and aged (24 mo. old) sedentary (SED) mice and following 2 wks of RW (24h wheel access) or TM training (45 min/day, 5 day/wk). Cardiorespiratory adaptations were assessed with pre‐ and post‐maximal treadmill tests. Maximal muscle force was lower in aged than young SED mice (1.1±0.04 vs. 1.6±0.07 g/kg BW, respectively, p&lt;0.05). In young groups, neither RW nor TM increased force over SED. In aged groups, RW and TM were associated with respective 22 and 26% higher maximal forces than aged SED mice (p&lt;0.05), but still were lower than young groups. Plantarflexor fatigue resistance was higher in aged than young SED mice (50±3 vs. 35±3% of max, respectively, p&lt;0.05) with no age differences in RW and TM groups. In treadmill pre‐tests, young groups ran longer than aged groups (9:23±0:52 vs. 5:09± 0:51, respectively p&lt;0.05). Increases in treadmill time after training occurred only in young and aged TM with respective 25:34±8:24 and 16:42±2:39 increases from pre to post test (p&lt;0.05). These findings suggest voluntary and prescribed exercise attenuate some age‐associated reductions in muscle force, but prescribed exercise is most effective in improving cardiorespiratory fitness in young and older mice.

One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and methylone

BackgroundExercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation. MethodsRats were trained in the intravenous self-administration (IVSA) of d-methamphetamine (METH; 0.05mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5mg/kg/inf) or methylone (0.5mg/kg/inf). Once IVSA was established, the effect of ∼22h of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design. ResultsProvision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual's decrease in drug intake. ConclusionsWheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern.

Wheel running decreases palatable diet preference in Sprague–Dawley rats

Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague–Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel access initially showed complete avoidance of the two palatable diets, the avoidance of the HS diet was transient. Experiment 2 demonstrated that male rats developed decreased HF diet preferences regardless of the order of diet and wheel running access presentation. Running associated changes in HF diet preference in females, on the other hand, depended on the testing schedule. In female rats, simultaneous presentation of the HF diet and running access resulted in transient complete HF diet avoidance whereas running experience prior to HF diet access did not affect the high preference for the HF diet. Ovariectomy in females resulted in HF diet preference patterns that were similar to those in male rats during simultaneous exposure of HF and wheel running access but similar to intact females when running occurred before HF exposure. Overall, the results demonstrated wheel running associated changes in palatable diet preferences that were in part sex dependent. Furthermore, ovarian hormones play a role in some of the sex differences. These data reveal complexity in the mechanisms underlying exercise associated changes in palatable diet preference.

Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice.

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in colitis, we hypothesized that VWR and FTR would differentially affect the gut microbiome. Mice (9-10/treatment) were randomly assigned to VWR, FTR, or sedentary home cage control (SED) for 6 wk. VWR were given running wheel access, whereas FTR ran on a treadmill for 40 min/day at 8-12 m/min, 5% grade. Forty-eight hours after the last exercise session, DNA was isolated from the fecal pellets and cecal contents, and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform. Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups (P < 0.01). Interestingly, the community structures of the three treatment groups clustered separately from each other in both gut regions (P < 0.05). Contrary to our hypothesis, the α-diversity metric, Chao1, indicated that VWR led to reduced bacterial richness compared with FTR or SED (P < 0.05). Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa. Of particular interest, Turicibacter spp., which has been strongly associated with immune function and bowel disease, was significantly lower in VWR vs. SED/FTR. These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice. These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region.

Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle-aged rats.

We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16–17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW−). The 9 RW+ rats averaged 83 m/day (range: 8–163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW− rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle.