Freewheel Running Research Articles

Quantitative evaluation of the motivation to access a running wheel or a water bath in farm mink

The purpose of the series of experiments presented here was to quantify the priorities of mink for swimming water and running wheel, respectively, by construction of demand functions for each of the two resources by use of operant conditioning techniques. In all the experiments, the mink were kept individually in experimental cages that could be equipped with either a box of swimming water, a running wheel, or both resources at the same time. Each water box or running wheel was presented with a connected lever response manipulandum. The mink worked on a fixed ratio (FR) schedule (5, 10, 20, 40 and 60) for access to the resource (the reward). Eight 1-year-old females of the colour type Scan Brown were used and the reward duration was 2 min. In experiment 1, the mink had access to only one of the two resources at the same time. In experiment 2 they had access to both resources at the same time, while in experiment 3 they could work for one of the resources while they were given free access to the alternative resource. Finally, experiment 4 tested running wheel against either full or empty water box as a control. There were no differences in the elasticity of the demand for swimming water and for a running wheel, indicating that mink value these two types of cage enrichment equally high. However, a higher intercept and consequently a larger area under the demand curve for wheel than for water show that mink use the wheel much more than the water. Simultaneous access to both resources did not affect the elasticity of either swimming water or running wheel. Furthermore, the mink did not increase their use of the free running wheel as the price of swimming water was increased, or their use of free swimming water as the price of running wheel increased. Therefore, the two resources did not appear to substitute for each other. Both a running wheel and swimming water were valued higher than access to an empty water box. The mink used the running wheel mainly during their normal activity periods, whereas the swimming water was primarily used in the morning when the mink were feed and the water box refilled. The motivation for using swimming water seems to decline rather quickly. Based on the lack of substitutability between the two resources and the different diurnal patterns, it is suggested that different motivations underlie the use of these two resources. Use of the running wheel may represent a motivation to perform locomotive activity whereas use of swimming water may represent other motivations, such as exploratory behaviour.

Stress reduces the neuroprotective effect of exercise in a rat model for Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disease of nigrostriatal dopamine (DA) neurons that project from the substantia nigra pars compacta (SNc) to the striatum. To further understand PD, researchers have developed standardized animal models of PD. In this study, Long Evans (LE) rats were unilaterally lesioned by injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle (MFB) of the left hemisphere. The rats were divided into three groups randomly; group 1 (runners) were housed in individual cages with attached running wheels, group 2 (stressed-runners) had access to individual free running wheels, except post-lesion when the rats were subjected to immobilization of the running wheel for 1 h per day for 14 days, as well as one session of 24-h food deprivation and a 7-h shift in the light/dark cycle. Group 3 (non-runnners) were housed individually in cages with attached running wheels that were permanently immobilized. Subcutaneous injection of the DA agonist, apomorphine, caused stressed-runners and non-runners to rotate vigorously away from the side of the lesion (contralaterally). Apomorphine-induced rotations provide a behavioural measure of the extent of the lesion, a depletion of more than 80% of DA neurons is required to produce vigorous contralateral rotations in response to apomorphine injection. Runners rotated significantly less than non-runners and stressed-runners. The number of rotations performed by stressed-runners was not significantly different from non-runners, suggesting that stress had cancelled the neuroprotective effect of running. Immunohistochemical staining for tyrosine hydroxylase in the SNc revealed slightly less destruction of DA neurons in the runners than in stressed-runners or non-runners, although these differences did not achieve statistical significance. The behavioural results confirm a previous finding suggesting that voluntary exercise is neuroprotective. A novel finding is that mild stressors cancel the neuroprotection afforded by voluntary exercise.

Freewheel running selectively prevents mouse CD4 + intestinal lymphocyte death produced after a bout of acute strenuous exercise

Aerobic exercise increases oxidant stress and leads to apoptosis of mouse intestinal lymphocytes (IL). The purpose of this study was to determine whether freewheel running prevents IL loss 24 h after a bout of strenuous exercise. Mice were randomly assigned to in-cage running wheels with 24 h access (WR) or individual cages without running wheels (NR) for 4 months. WR mice accumulated 364 km over 4 months and had higher cytochrome oxidase activity in the plantaris ( p < .05), indicative of training. Total intestinal, CD3αβ, CD3γδ, CD8α, and CD8β lymphocytes and intracellular glutathione were significantly lower in WR and NR mice 24 h post-exercise. The number of CD4 IL decreased 24 h after exercise in NR ( p < .01) but not in WR mice relative to their respective no exercise controls. Thus, freewheel running in mice for 4 months prevented CD4 IL loss after acute exercise.

Physical activity alters the brain Hsp72 and IL-1β responses to peripheralE. colichallenge

Physically active rats have facilitated heat shock protein 72 (Hsp72) responses after stressor exposure in both brain and peripheral tissues compared with sedentary rats. This study verifies that physically active animals do not have elevated Hsp72 levels compared with sedentary animals in the hypothalamus, pituitary, or dorsal vagal complex. We then examined whether 1) physically active rats respond more efficiently than sedentary rats to a bacterial challenge; 2) peripheral immune challenge elicits brain induction of Hsp72; 3) this induction is facilitated by prior freewheel running; and 4) Hsp72 upregulation produced by peripheral immune challenge results in a commensurate decrease in the proinflammatory cytokine IL-1beta. Adult male Fischer 344 rats were housed with either a mobile or locked running wheel. Six weeks later, rats were injected intraperitoneally with saline or Escherichia coli and killed 30 min, 2.5 h, 6 h, and 24 h later. Serum endotoxin and IL-1beta, and peritoneal fluid endotoxin and E. coli colony-forming units (CFUs) were measured. Hsp72 and IL-1beta were measured in hypothalamus, pituitary, and dorsal vagal complex. The results were that physically active rats had a faster reduction in endotoxin and E. coli CFUs and lower levels of circulating endotoxin and cytokines compared with sedentary rats. E. coli challenge elicited significantly greater time-dependent increases of both Hsp72 and IL-1beta in hypothalamus, pituitary, and dorsal vagal complex of physically active animals but not sedentary animals. Contrary to our hypothesis, increases in Hsp72 were positively correlated with IL-1beta. This study extends our findings that physical activity facilitates stress-induced Hsp72 to include immunological stressors such as bacterial challenge and suggests that brain Hsp72 and IL-1beta responses to peripheral immune challenge may contribute to exercise-mediated resistance to long-term sickness.

Resting Cellular and Physiological Effects of Freewheel Running

Exercise modulates many aspects of physiology. The purpose of the current experiment was to characterize the impact of regular, moderate physical activity on resting, baseline measures of cellular immunity blood lipids, and muscle enzyme. Male Fischer 344 rats were housed with either mobile (run, N = 10) or immobile (sedentary, N = 10) running wheels. After 4 wk of running, rats were sacrificed. Blood and muscle (long and medial heads of the triceps) were collected. From blood, white blood cell (WBC) differentials, red blood cell (RBC) count, hemoglobin, hematocrit, and lipid profiles were measured. Muscle citrate synthase (CS) activity was measured by spectrophotometric analysis. Rats ran an average of 9.89 +/- 0.79 km.wk(-1). There were no differences in the total number of circulating WBC, RBC, or eosinophils. Freewheel running decreased the number of circulating neutrophils (P < 0.001), monocytes (P < 0.01), and basophils (P < 0.01), while increasing the number of lymphocytes (P < 0.001), when compared with sedentary animals. Mean corpuscular content of hemoglobin was elevated in the freewheel group (P < 0.01). Physically active animals had slightly lower triglycerides and LDL, and elevated HDL. These changes resulted in a significant improvement in LDL/HDL ratio (P < 0.05). Muscle CS activity was unchanged between groups. Both the alterations in the RBC hemoglobin and lipid proteins are positive health changes associated with exercise training. The impact of the alterations in WBC differentials remains unknown but could indicate a reduction in inflammatory load. In conclusion, freewheel running provides sufficient exercise stimulus to produce some, but not all, training associated physiological adaptations.

Habituation contributes to the decline in wheel running within wheel-running reinforcement periods

Habituation appears to play a role in the decline in wheel running within an interval. Aoyama and McSweeney [Aoyama, K., McSweeney, F.K., 2001. Habituation contributes to within-session changes in free wheel running. J. Exp. Anal. Behav. 76, 289-302] showed that when a novel stimulus was presented during a 30-min interval, wheel-running rates following the stimulus increased to levels approximating those earlier in the interval. The present study sought to assess the role of habituation in the decline in running that occurs over a briefer interval. In two experiments, rats responded on fixed-interval 30-s schedules for the opportunity to run for 45 s. Forty reinforcers were completed in each session. In the first experiment, the brake and chamber lights were repeatedly activated and inactivated after 25 s of a reinforcement interval had elapsed to assess the effect on running within the remaining 20 s. Presentations of the brake/light stimulus occurred during nine randomly determined reinforcement intervals in a session. In the second experiment, a 110 dB tone was emitted after 25 s of the reinforcement interval. In both experiments, presentation of the stimulus produced an immediate decline in running that dissipated over sessions. No increase in running following the stimulus was observed in the first experiment until the stimulus-induced decline dissipated. In the second experiment, increases in running were observed following the tone in the first session as well as when data were averaged over several sessions. In general, the results concur with the assertion that habituation plays a role in the decline in wheel running that occurs within both long and short intervals.

Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c-fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats

Modulation of sympathetic drive to the spleen is one potential mechanism whereby physical activity prevents stress-induced splenic immune suppression in rats. The current study tested the hypothesis that voluntary freewheel running reduces peripheral sympathetic drive by modulating stress-induced activity of brain regions synaptically linked to sympathetically innervated peripheral organs, including the adrenals and spleen. To this end, adrenal and splenic catecholamine content and activity of the central sympathetic circuit indexed by c-Fos protein induction, elicited by acute exposure to inescapable tail shock, were measured. Stressor exposure depleted adrenal and splenic norepinephrine content and elicited a robust increase in c-Fos in the brains of sedentary rats. Physical activity status had no effect on adrenal norepinephrine content. Indicative of attenuated sympathetic drive to the spleen, however, 6 weeks of voluntary freewheel running diminished stress-induced splenic norepinephrine depletion, and significantly attenuated stress-induced c-Fos in specific brain regions responsible for sympathetic regulation, including tyrosine hydroxylase-immunoreactive neurons of the locus coeruleus, A5 cell group and rostral ventrolateral medulla. Results suggest that voluntary activity attenuates sympathetic drive to the spleen during stressor exposure by selectively modulating stress-induced activity of the central sympathetic circuit. The attenuation of sympathetic responses observed in this study may be one important mechanism for the protective effect of physical activity against stress-related illness and immunosuppression.

Freewheel Running Prevents Learned Helplessness/Behavioral Depression: Role of Dorsal Raphe Serotonergic Neurons

Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) are implicated in mediating learned helplessness (LH) behaviors, such as poor escape responding and expression of exaggerated conditioned fear, induced by acute exposure to uncontrollable stress. DRN 5-HT neurons are hyperactive during uncontrollable stress, resulting in desensitization of 5-HT type 1A (5-HT1A) inhibitory autoreceptors in the DRN. 5-HT1A autoreceptor downregulation is thought to induce transient sensitization of DRN 5-HT neurons, resulting in excessive 5-HT activity in brain areas that control the expression of learned helplessness behaviors. Habitual physical activity has antidepressant/anxiolytic properties and results in dramatic alterations in physiological stress responses, but the neurochemical mediators of these effects are unknown. The current study determined the effects of 6 weeks of voluntary freewheel running on LH behaviors, uncontrollable stress-induced activity of DRN 5-HT neurons, and basal expression of DRN 5-HT1A autoreceptor mRNA. Freewheel running prevented the shuttle box escape deficit and the exaggerated conditioned fear that is induced by uncontrollable tail shock in sedentary rats. Furthermore, double c-Fos/5-HT immunohistochemistry revealed that physical activity attenuated tail shock-induced activity of 5-HT neurons in the rostral-mid DRN. Six weeks of freewheel running also resulted in a basal increase in 5-HT1A inhibitory autoreceptor mRNA in the rostral-mid DRN. Results suggest that freewheel running prevents behavioral depression/LH and attenuates DRN 5-HT neural activity during uncontrollable stress. An increase in 5-HT1A inhibitory autoreceptor expression may contribute to the attenuation of DRN 5-HT activity and the prevention of LH in physically active rats.

Habitual physical activity facilitates stress-induced HSP72 induction in brain, peripheral, and immune tissues.

The mechanism(s) for how physically active organisms are resistant to many damaging effects of acute stressor exposure is unknown. Cellular induction of heat-shock proteins (e.g., HSP72) is one successful strategy used by the cell to survive the damaging effects of stress. It is possible, therefore, that the stress-buffering effect of physical activity may be due to an improved HSP72 response to stress. Thus the purpose of the current study was to determine whether prior voluntary freewheel running facilitates the stress-induced induction of HSP72 in central (brain), peripheral, and immune tissues. Adult male Fischer 344 rats were housed with either a mobile running wheel (Active) or a locked, immobile wheel [sedentary (Sed)] for 8 wk before stressor exposure. Rats were exposed to either inescapable tail-shock stress (IS; 100 1.6-mA tail shocks, 5-s duration, 60-s intertrial interval), exhaustive exercise stress (EXS; treadmill running to exhaustion), or no stress (controls). Blood, brain, and peripheral tissues were collected 2 h after stressor termination. The kinetics of HSP72 induction after IS was determined in cultured mesenteric lymph node cells. Activation of the stress response was verified by measuring serum corticosterone (RIA). Tissue and cellular HSP72 content were measured using HSP72 ELISA in cell lysates. Both Active and Sed rats had elevated levels of serum corticosterone after stress. In contrast, Active but not Sed rats exposed to IS and/or EXS had elevated HSP72 in dorsal vagal complex, frontal cortex, hippocampus, pituitary, adrenal, liver, spleen, mesenteric lymph nodes, and heart. In addition, Active rats exposed to IS demonstrated a faster induction of lymphocyte HSP72 compared with Sed rats. Thus Active rats responded to stress with both greater and faster HSP72 responses compared with Sed rats. These results indicate that previous physical activity potentiates HSP72 expression after a wide range of stressors. Facilitated induction of HSP72 may contribute to the increased stress resistance previously reported in physically active organisms.

Increased serum nIgM in voluntarily physically active rats: a potential role for B-1 cells.

Moderate, habitual physical activity improves health, possibly because of beneficial changes in immune function. For example, physical activity can increase natural killer cell cytotoxicity, T cell proliferation, and macrophage function but has minimal impact on antigen-driven B-2-mediated immunoglobulin (Ig) responses. The following studies tested whether physical activity selectively impacts nonantigen-driven B-1-natural IgM (nIgM) but not antigen-driven B-2 Ig. Adult male, pathogen-free Sprague-Dawley rats in a barrier facility voluntarily ran in wheels from 7 to 56 days or were housed in an enriched environment for 56 days. Rats received either no antigen or keyhole limpet hemocyanin (KLH) to assess the B-2 response. Blood samples assessed serum nIgM, total IgG, total serum protein, anti-KLH IgM, and anti-KLH IgG. Physically active rats had higher serum nIgM after 7 days of running, and nIgM remained elevated over 56 days of running. In contrast, free-wheel running produced no changes in total IgG, total serum protein, anti-KLH IgM, and anti-KLH IgG. Environmental enrichment did not alter immune measures from controls. These results suggest that B-1, not B-2, cell responses are selectively impacted by physical activity. Because nIgM is important in multiple aspects of the immune response, an elevation in this innate humoral component could contribute to improved immunity in physically active organisms.

HABITUATION CONTRIBUTES TO WITHIN‐SESSION CHANGES IN FREE WHEEL RUNNING

Three experiments tested the hypothesis that habituation contributes to the regulation of wheel running. Rats ran in a wheel for 30-min sessions. Experiment 1 demonstrated spontaneous recovery. Rats ran more and the within-session decreases in running were smaller after 2 days of wheel deprivation than after 1 day. Experiment 2 demonstrated dishabituation. Running rate increased immediately after the termination of a brief extra event (application of the brake or flashing of the houselight). Experiment 3 demonstrated stimulus specificity. Rats completed the second half of the session in either the same wheel as the first half, or a different wheel. Second-half running was faster in the latter case. Within-session patterns of running were well described by equations that describe data from the habituation, motivation, and operant literatures. These results suggest that habituation contributes to the regulation of running. In fact, habituation provides a better explanation for the termination of wheel running than fatigue, the variable to which this termination is usually attributed. Overall, the present findings are consistent with the proposition that habituation and sensitization contribute to the regulation of several forms of motivated behavior.

Investigation into the regulation of the circadian system by dopamine and melatonin in the adult Siberian hamster (Phodopus sungorus).

Dopamine and melatonin have both been implicated in mediating maternal influences on the developing circadian system of altricial rodents. The aim of these studies was to investigate their role in the entrainment of the circadian system of the adult Siberian hamster (Phodopus sungorus). In-situ hybridization revealed that D1-dopamine receptor (D1-R) mRNA was expressed in the adult suprachiasmatic nucleus (SCN) at levels comparable to neonates. As dopamine has been postulated to mimic photic stimulation during early development, experiment 1 compared the effects of a D1-R agonist and a light pulse on free-running wheel running rhythms in hamsters maintained in constant dim red light. A phase response curve to light was generated, revealing clear phase delays early in the subjective night, and large phase advances in the late subjective night. However, the D1-R agonist (SKF 81297, 2 mg/kg, s.c.) did not produce consistent phase shifts at any circadian phase. Experiment 2 tested the ability of this dopaminergic agonist to modulate photic responses of the circadian system. Free-running animals were pre-treated with SKF 81297 (2 mg/kg, s.c.) 30 min before a 15 min light pulse given early or late in the subjective night. This agonist had no effect on the magnitude of phase shifts at either circadian time. In experiment 3, light pulses at CT13-15 induced expression of the immediate early gene c-fos in the SCN, as assessed by immunocytochemistry for the protein product. In contrast, SKF 81297 (2 mg/kg, s.c.) at the same phase did not induce c-fos in the SCN, despite marked c-fos induction in the caudate-putamen, nor did it affect photic induction of c-fos in the SCN. To investigate whether dopamine might be involved in nonphotic regulation of the circadian system in adult hamsters, experiment 4 compared the response of free-running hamsters to a series of injections of SKF 81297 (2 mg/kg, s.c.) or melatonin (1 mg/kg, s.c.), since melatonin receptor expression in the SCN also persists into adulthood. Animals were treated every 23.5 h for 6 days. The serial injections of melatonin produced cumulative phase advances of up to 3 h when delivered in late subjective day, but not when presented in late subjective night. Hamsters did not respond to SKF 81297 or vehicle treatment at either circadian phase. Moreover, pre-treatment with the dopaminergic agonist did not affect the phase-advancing effects of melatonin when both were given in the serial injection protocol. These results demonstrate clear phase-dependent effects of light pulses and melatonin on circadian rhythms in Siberian hamsters, but suggest that D1-Rs in the SCN no longer modulate photic or melatonin-dependent entrainment pathways in the adult.

Weight cycling alters the effects of D -fenfluramine on susceptibility to activity-based anorexia

It has been proposed that anorexia nervosa (AN) is treatable with serotonergic (5-HT) agonists. It seems paradoxical to treat a disorder characterized by reduced food intake with appetite suppressants. The effects of the indirect-acting 5-HT agonist D-fenfluramine on activity-based anorexia (ABA) were investigated, coincident with ABA (experiment 1), and after tolerance and weight cycling (experiment 2). Rats were chronically infused with D-fenfluramine by using subcutaneous mini-pumps and then tested for susceptibility to ABA (22.5 h free running wheel access, 1.5 h access to food). Concurrent D-fenfluramine increased the risk of ABA by decreasing food consumption. Conversely, D-fenfluramine reduced the incidence of ABA in tolerant rats with a history of weight cycling. Therefore, the effects of D-fenfluramine depend on whether drug administration coincides with ABA or whether tolerance and weight cycling precede ABA onset. The results were related to the metabolic effects of weight cycling and the treatment of anorexia nervosa.

Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions

Article de synthese sur l'efflux des neurotransmetteurs catecholaminergiques chez les mammiferes. Origine des catecholamines: la noradrenaline, l'adrenaline et la dopamine dans le plasma et l'urine. Decharge de ces catecholamines dans le corps entier et dans les differents organes. Etude des determinants de la decharge de la noradrenaline des nerfs sympathiques vers la circulation. Utilisation des mesures du taux de decharge dans l'estimation du mode de decharge des nerfs