Change In Ambulatory Activity Research Articles

Naringenin Supplementation to a Chow Diet Enhances Energy Expenditure and Fatty Acid Oxidation, and Reduces Adiposity in Lean, Pair-Fed Ldlr-/- Mice.

Naringenin is a citrus-derived flavonoid that has potent lipid-lowering and insulin-sensitizing effects in obese mouse models of metabolic dysfunction. However, in these models, a significant effect of naringenin supplementation is the prevention of weight gain, which in itself can confer metabolic protection. Therefore, in the present study, the effect of naringenin supplementation in lean, chow-fed Ldlr-/- mice is investigated. In Ldlr-/- mice with isocaloric food consumption, treatment with naringenin for 8 weeks reduces body weight and adiposity compared to littermate controls pair-fed the chow diet alone. Furthermore, naringenin treatment reduces plasma lipids and enhances insulin sensitivity compared to chow-fed controls. Metabolic cage studies reveal that naringenin-treated mice have elevated energy expenditure with no change in ambulatory activity. Additionally, naringenin-treated mice have an increased respiratory exchange ratio and food consumption during the dark cycle. Treatment increases the expression of fatty acid oxidation genes in liver, and increased β-hydroxybutyrate concentrations in plasma, indicating that one mechanism through which naringenin mediates metabolic improvement is enhanced hepatic fatty acid oxidation. These studies highlight the potential therapeutic utility of naringenin and suggest that this flavonoid maintains potent metabolic properties in the absence of obesity or a high-fat diet.

Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis

The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain. We investigated whether baseline and change in objectively-assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance. We assessed prospective data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January, 2002, and January, 2004. Participants also either had existing cardiovascular disease (if age ≥50 years) or at least one additional cardiovascular risk factor (if age ≥55 years). Participants were followed-up for cardiovascular events (defined as cardiovascular mortality, non-fatal stroke, or myocardial infarction) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months. Adjusted Cox proportional hazard models quantified the association of baseline and change in ambulatory activity (from baseline to 12 months) with the risk of a subsequent cardiovascular event, after adjustment for each other and potential confounding variables. This study is registered with ClinicalTrials.govNCT00097786. During 45,211 person-years follow-up, 531 cardiovascular events occurred. Baseline ambulatory activity (hazard ratio [HR] per 2000 steps per day 0·90, 95% CI 0·84-0·96) and change in ambulatory activity (0·92, 0·86-0·99) were inversely associated with the risk of a cardiovascular event. Results for change in ambulatory activity were unaffected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months. In individuals at high cardiovascular risk with impaired glucose tolerance, both baseline levels of daily ambulatory activity and change in ambulatory activity display a graded inverse association with the subsequent risk of a cardiovascular event. Novartis Pharmaceuticals.

Effect of berberine on depression- and anxiety-like behaviors and activation of the noradrenergic system induced by development of morphine dependence in rats.

The purpose of this study was to evaluate whether berberine (BER) administration could attenuate depression- and anxiety-like behaviors and increase corticotrophin-releasing factor (CRF) and tyrosine hydroxylase (TH) expression following chronic morphine withdrawal in rats. Male rats were exposed to chronic, intermittent, escalating morphine (10~50 mg/kg) for 10 days. After the last morphine injection, depression- and anxiety-like beahvior associated with morphine discontinuation persisted for at least three days during withdrawal without any change in ambulatory activity. Daily BER administration significantly decreased immobility in the forced swimming test and increased open-arm exploration in the elevated plus maze test. BER administration also significantly blocked the increase in hypothalamic CRF expression and TH expression in the locus coeruleus (LC) and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression. Taken together, these findings demonstrated that BER administration significantly reduced morphine withdrawal-associated behaviors following discontinuation of repeated morphine administration in rats, possibly through modulation of hypothalamic CRF and the central noradrenergic system. BER may be a useful agent for treating or alleviating complex withdrawal symptoms and preventing morphine use relapses.

Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson’s disease

Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity.

The effect of increased ambulatory activity on markers of chronic low‐grade inflammation: evidence from the PREPARE programme randomized controlled trial

To investigate whether an exercise intervention programme, with or without pedometer use, is effective at reducing chronic low-grade inflammation in those with impaired glucose tolerance. Using baseline and 12-month data from the Pre-diabetes Risk Education and Physical Activity Recommendation and Encouragement (PREPARE) programme randomized controlled trial, we investigated whether the pedometer or the standard version of the PREPARE programme is associated with reduced chronic low-grade inflammation. Outcomes included interleukin-6, C-reactive protein, fasting and 2 h post-challenge glucose values and objectively measured ambulatory activity. Seventy-four participants (31% female; mean age, 65 years; body mass index, 29.3 ± 4.8 kg/m(2) ) were included, of which 26 were in the control group and 24 were in each intervention group. At 12 months there was an increase in ambulatory activity of 1351 and 1849 steps/day in the standard and pedometer group, respectively, compared with control conditions; however, there was no significant change in markers of chronic low-grade inflammation. Across the pooled study sample, change in ambulatory activity was significantly correlated with change in interleukin-6 (r = -0.32, P = 0.01) after adjustment for group, age, sex, ethnicity, aspirin and statin medication, baseline body mass index and change in body mass index. Change in interleukin-6 was also significantly correlated with change in 2 h glucose after adjustment for the same variables (r = 0.26, P = 0.03). This study failed to show reductions in markers of chronic low-grade inflammation following an intervention that promoted modest increases in ambulatory activity; however, across the study sample, increased ambulatory activity was associated with reduced interleukin-6, independent of obesity.

Dihydromagnolol – a Potent Anxiolytic-like Agent in Mice

Oral administration of a single 1 mg/kg dose of dihydromagnolol [DHM; 5'-(2-propenyl)-5-propyl-(1,1'-biphenyl)- 2,2'-diol] produced a significant anxiolytic-like effect in mice, as assessed in an elevated plus-maze test. This dose did not cause any marked change in ambulatory activity. The anxiolytic-like effect peaked at 1 h and persisted for more than 3 h after administration. Significant anxiolytic-like activity at a dose of 1 mg/kg of dihydromagnolol was also indicated by use of Vogel’s conflict test. Although dihydromagnolol enhanced 36 Cl - uptake into mouse cortical synaptoneurosomes in the absence of muscimol in in vitro experiments, it did not alter the activities of diazepam, flumazenil or bicuculline in vivo. The results of these studies suggest that the anxiolytic-like activity of DHM occurs through action at a site(s) in the nervous system other than the GABA A /benzodiazepine receptor complex which is the site of action of the traditional benzodiazepine anxiolytics.

Withdrawal from chronic morphine administration causes prolonged enhancement of immobility in rat forced swimming test.

Opiate-dependent subjects experience severe depression as one of the subjective symptoms during withdrawal. No experimental work, however, has focused on the ability of opiate-withdrawal to produce depression-like behavior in dependent animal. OBJECTIVES. We therefore investigated whether withdrawal from chronic morphine treatment affects immobility in forced swimming test in rats. Morphine was administered in a dose escalation fashion using doses ranging from 20 to 140 mg/kg twice daily for 14 days, followed by 1-6 days of withdrawal, and their duration of immobility was assessed. After the last morphine treatment. an increase in immobility occurred late on day 3 and persisted to at least day 6 of withdrawal without any change in ambulatory activity. The results suggest that the morphine withdrawal resulted in prolonged enhancement of depression-like behavior in drug-dependent laboratory animals.

Feeding behavior and ambulatory activity in rats with d-galactosamine-induced hepatic failure

This study was undertaken to investigate changes in feeding behavior and ambulatory activity, in rats with d-galactosamine ( d-GAL)-induced hepatic failure. d-GAL was administered (1000 mg/kg) IP at 1800, just before the dark phase. The first significant decrease of ambulatory activity in rats with hepatic failure was observed between 0000 and 0300 h. A significant increase in drinking behavior was observed between 1800 and 2100 h, and a significant decrease was observed between 2100 and 0300 h. A significant decrease in food intake occurred between 1800 and 2400 h. Thereafter, there was no difference in food intake. In conclusion, we demonstrated significant changes in ambulatory activity, drinking behavior and food intake produced by d-GAL. A wide variation in systems, including monoamine turnover, and amino acid disturbance could be expected in these animals, and such changes might also have contributed to the results observed.

Changes in ambulatory activity and dopamine turnover in streptozotocin-induced diabetic rats.

We have observed the acute effects of streptozotocin (STZ) on ambulatory activity by employing the automatic apparatus for continuous and direct measurement of drinking and ambulation. Ambulatory activity (counts) in the control periods was 298.2 +/- 20.1 in the dark, 35.6 +/- 9.4 in the light, and 343.9 +/- 24.1 over 24 h. After administration of STZ (60 mg/kg, ip), the ambulatory activity gradually decreased [at 3 days: 165.0 +/- 12.3 in the dark (P less than 0.001), 34.0 +/- 10.5 in the light (P = NS), and 199.0 +/- 10.5 over 24 h (P less than 0.001). For determination of statistical significance, values were compared with those at the same time in the control groups. We observed decreased ambulatory activity in STZ-induced diabetic rats during the dark, but not the light, cycle. Moreover, ambulatory activity in STZ-induced diabetic rats gradually decreased, while the blood glucose level rose. Ambulatory activity correlated inversely with blood glucose level (r = -0.76; P less than 0.05). We measured the ratio of dopamine (DA) to 3,4-dihydroxyphenylacetic acid (nanograms per g) in the striatum. The turnover rate of DA was significantly lower in the diabetic rats than in the control group [diabetic, 0.102 +/- 0.003; control, 0.112 +/- 0.001 (mean +/- SE); P less than 0.05]. A negative correlation between the 3,4-dihydroxyphenylacetic acid to DA ratio and blood glucose level was observed (r = -0.693; P less than 0.01). The present study suggests that there are metabolic abnormalities in the striatum dopaminergic neurons of STZ-induced diabetic rats associated with decreased ambulatory activity.

Behavioral effects of propentofylline (HWA 285) on ambulatory activity, discrete avoidance response and passive avoidance response in mice

Behavioral effects of propentofylline (HWA 285) were investigated by means of ambulatory activity, discrete lever-press avoidance and step-through type passive avoidance response in mice. Single administration of HWA 285 produced no marked change in the bodily condition and also produced no changes in ambulatory activity at 1.25-20 mg/kg, s.c.; the discrete avoidance response at 2.5-40 mg/kg, s.c.; and the passive avoidance response at 10-30 mg/kg, s.c. However, 5-20 mg/kg of HWA 285 attenuated the ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). HWA 285 tended to attenuate the avoidance-suppressing effect of chlorpromazine (2 mg/kg, s.c.) and physostigmine (0.1 mg/kg, s.c.) at 2.5 mg/kg, while it enhanced the effect of chlorpromazine at 10-40 mg/kg. The mice treated with HWA 285 (10-30 mg/kg) at 30 min before or immediately after the acquisition trial did not show a marked change in the passive avoidance response when the retention trial was done 24 hr after the acquisition trial. The treatment with scopolamine (2 mg/kg, s.c.) at 30 min before the acquisition trial suppressed the passive avoidance response, eliciting a marked shortening of the step-through latency and decrease in % of mice to the 300 sec criterion of latency. The effect of scopolamine was attenuated by combined administration of HWA 285 (30 mg/kg) and treatment with HWA 285 (30 mg/kg) after the end of the acquisition trial. The present results suggest that HWA 285 demonstrates complex behavioral effects which vary dependently on the doses and types of behaviors.

Effects of amiridin on ambulatory activity and the discrete shuttle avoidance response in mice

Behavioral effects of amiridin, [9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta (b)-quinoline monohydrate hydrochloride] were investigated by observing ambulatory activity and the discrete shuttle avoidance response in mice. In addition, the in vivo effects of 4-amino-pyridine and physostigmine, which have inhibitory effects similar to those of amiridin on acetylcholine esterase in vitro, were compared with those of amiridin. Single doses of amiridin (0.3-10 mg/kg, s.c.) or 4-aminopyridine (0.3-3 mg/kg, s.c.) failed to produce marked changes in ambulatory activity, nor did these drugs exhibit any antagonistic effect on the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.). However, single doses of physostigmine (0.03-0.1 mg/kg, s.c.) suppressed the ambulatory activity and antagonized with scopolamine. Amiridin (1-3 mg/kg, s.c. and 0.3-1 mg/kg, p.o.) and 4-aminopyridine (1-3 mg/kg, s.c.) administered to mice immediately before the training start of the discrete shuttle avoidance response facilitated the acquisition process. Furthermore, amiridin, but not 4-aminopyridine, elicited a good retention of the avoidance response after 24 hr. Although amiridin and 4-aminopyridine facilitated acquisition of the avoidance response, they failed to affect an avoidance response which had been established by sufficient previous training. On the other hand, physostigmine (0.1 mg/kg, s.c.) not only retarded acquisition of the avoidance response, but also suppressed established avoidance responses. The present results suggest that amiridin facilitates both acquisition and memory processes of mice in the discrete shuttle avoidance situation without eliciting a marked change in general activity level.

Circadian variation in methamphetamine- and apomorphine-induced increase in ambulatory activity in mice.

The existence of circadian variation in methamphetamine- and apomorphine-induced change in ambulatory activity in mice was investigated. Adult male mice of dd strain, which had been housed on a 12 hr light-dark schedule (light period; 6:00-18:00) for 4 weeks, received injections of either methamphetamine HCl 1 or 2 mg/kg SC at one of six times of day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), or apomorphine HCl 0.5 or 1 mg/kg SC at one of six times of day (3:30, 7:30, 11:30, 15:30, 19:30 and 23:30). The control animals were administered a physiological saline vehicle alone at the corresponding times of day. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 3 hr after methamphetamine, and for 1 hr after apomorphine. A circadian variation in the ambulatory activity was observed after the administration of the saline, methamphetamine and apomorphine. Here, the highest activity counts were found when the saline, methamphetamine and apomorphine were administered during the late dark period (3:00 or 3:30), while the lowest activity counts were found when the saline and apomorphine 1 mg/kg were administered during the mid light period (11:00 or 11:30), and methamphetamine 1 and 2 mg/kg and apomorphine 1 mg/kg were administered during the late light period (15:00 or 15:30). The circadian variation in methamphetamine-induced increase in the activity was abolished by a pretreatment with reserpine 2 mg/kg SC 4 hr before, but that of apomorphine was maintained even by the pretreatment with reserpine. The present results suggest that the methamphetamine- and apomorphine-induced increase in the ambulatory activity in mice is dependent on the time-of-day of the drug administration, and the occurrence is mainly due to a circadian variation in activity of the catecholaminergic systems in the brain.

Changes in ambulatory activities and muscle relaxation in rats after repeated doses of diazepam.

Changes in rat ambulatory activity and muscle tone after diazepam treatments (2.5, 5, 10, and 20 mg/kg orally) were compared under single and repeated (for 2, 4, 7, and 14 days) administration schedules. Ambulatory activity in the open field test was enhanced by a single dose of 2.5 mg/kg and reduced by 20 mg/kg. However, after all repeated treatment schedules, diazepam resulted in dose-dependent elevations of activity. Even with a treatment period of only 2 days, 20 mg/kg diazepam produced a marked increase in ambulation, which became more conspicuous with increases in the treatment periods. Acutely administered diazepam produced a dose-dependent reduction in muscle tone, but tolerance was noted to this effect during repeated administrations. Thus, time- and dose-dependent increases in ambulation during repeated treatments with diazepam can be partially explained by time-dependent tolerance development to its muscle relaxant effects. The enhancement in ambulation after short-term repetitive dosings of benzodiazepines can be used as a simple indicator for detecting their disinhibitory potentials.

Further Aspects of Aggressive Behavior Induced by Sustained High Dose of Theophylline in Rats*

Sustained injection with a high dose of theophylline increased aggressiveness in rats in both behavioral ratings and paired fighting. In the latter test, 50% of theophyllinized pairs took the fighting position following a hand-clap and the 75% of treated rats were dominant over control partners. In the open field test, the theophyllinized rat discharged fewer boluses, but there was no change in ambulatory activity. The present results support the finding in our previous study that demonstrated the production of affective aggression with the chronic treatment of theophylline.