Weeks Of Endurance Exercise Research Articles

264-LB: Aerobic Exercise Training Reorganizes Skeletal Muscle Mitochondrial and Lipid Droplet Architecture

Exercise is a known intervention to alleviate insulin resistance. This study investigated how a 12-week endurance exercise intervention changes skeletal muscle mitochondrial and lipid droplet architecture in patients with type 2 diabetes. Participants completed 12 weeks of endurance exercise at 70% of their VO2 max five days a week at one hour a day. Muscle biopsies were taken before and 72 hours after the last exercise session. A subset of these muscle biopsies from two participants (58±0 years, 42.3±3.3 BMI, 2.5±0.7 medications, 8.2±0.1% HbA1c) was imaged using focused ion-beam scanning electron microscopy. Due to these results being preliminary, general trends are discussed. A deep-learning model segmented 14,197 mitochondria and 4,400 lipid droplets to assess individual mitochondrial and lipid droplet 3D structures, and mitochondria-to-lipid interactions. Surprisingly, exercise did not change individual mitochondrial and lipid droplet volume, surface area to volume ratio, or sphericity. There was an increase in mitochondria-to-mitochondria and mitochondria-to-lipid droplet interactions after endurance training. These preliminary data suggest that exercise may relieve insulin-resistant skeletal muscle by increasing the connectivity among mitochondria and lipid droplets prior to changing individual organelle morphology. Further analyses are ongoing to confirm these findings. Disclosure H. A. Parry: None. C. L. Axelrod: None. V. Baena: None. W. S. Dantas: None. J. P. Kirwan: None. B. Glancy: None.

The effect of endurance exercise and rosehip extract supplementation on the expression of P53 and cytochrome C genes in male rat heart.

Introduction: Considering the effect of apoptosis on cardiovascular disease, this study aimed to determine the combined effect of endurance exercise and rosehip extract supplementation on the expression of P53 and cytochrome C genes in the myocardium of male rats. Methods: A total of 35 male rats were randomly divided into five groups (n=7) as follows: endurance exercise+rosehip extract supplementation (Ex+Supp), endurance exercise (Ex), rosehip extract supplementation (Supp), six-month control (Con2), and three-month control (Con). The subjects in Ex+Supp and Ex groups performed endurance exercise (running on a treadmill at 24-33 m/min for 10-60 min) for 12 weeks, five times a week. Subjects in Ex+Supp and Supp groups consumed 1000 milligrams/ kilogram of rosehip extract for 12 weeks. Also, Con and Con2 groups did not receive any intervention. To RNA extraction and synthesis cDNA and evaluate the P53 and cytochrome C genes of the myocardium of rats, RT-PCR analysis was used. Results: Neither endurance exercise nor rosehip alone nor together significantly affected the expression of cytochrome C and P53 genes in the heart muscle of male rats (P>0.05). Also, endurance exercise (P=0.001) and rosehip supplementation (P=0.002) alone and in interaction (P<0.01) had a significant effect on body weight, myocardium weight, and the ratio of myocardium weight to body weight in male rats. Conclusion: Twelve weeks of endurance exercise accompanied with rosehip extract did not significantly affect the expression of P53 and cytochrome C genes. Further studies are suggested to confirm these results.

Effect of Endurance Exercise and Methamphetamine Administration on the Expression of Blood-Brain Barrier Related Factors and BDNF in Hippocampus of Male Sprague-Dawley Rat

PURPOSE: This study aimed to investigate the effect of short-term endurance exercise and methamphetamine administration on bloodbrain barrier (BBB)-related marker and brain-derived neurotrophic factor (BDNF) in the hippocampus of male Sprague-Dawley (SD) rats.METHODS: Forty male SD-rats were randomly assigned to 4 groups and treated for 2 weeks. For the methamphetamine group, 1 mg/ kg (+)-S-Methamphetamine hydrochloride (METH) was intraperitoneally injected daily, and an endurance exercise was performed at 21 m/min for 60 minutes. All treatments were performed daily, and METH or saline was administered after exercise. After 2 weeks of treatment, the head was decapitated under anesthesia, and the hippocampus was separated for western blotting.RESULTS: Two weeks of endurance exercise significantly increased the expression of occludin and claudin-5 in the hippocampus of the rats. Similarly, phosphorylation of CREB/BDNF and AKT/GSK3 signaling pathways were significantly increased. This phenomenon was also observed in the exercise and METH co-treatment groups. However, the single treatment of 1 mg/kg METH did not affect tight junction protein and BDNF expression.CONCLUSIONS: Endurance exercise increased the expression of BBB-related proteins and neurogenesis-related molecules, which were not inhibited by METH administration.

Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle.

Endurance exercise triggers skeletal muscle adaptations, including enhanced insulin signaling, glucose metabolism, and mitochondrial biogenesis. However, exercise-induced skeletal muscle adaptations may not occur in some cases, a condition known as exercise resistance. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite and has detrimental effects on the body such as causing diabetic complications, mitochondrial dysfunction, and inflammation. This study aimed to clarify the effect of methylglyoxal on skeletal muscle molecular adaptations following endurance exercise. Mice were randomly divided into four groups (n = 12/group): sedentary control group, voluntary exercise group, MG-treated group, and MG-treated with voluntary exercise group. Mice in the voluntary exercise group were housed in a cage with a running wheel, whereas mice in the MG-treated groups received drinking water containing 1% MG. Four weeks of voluntary exercise induced several molecular adaptations in the plantaris muscle, including increased expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), mitochondria complex proteins, Toll-like receptor 4 (TLR4), 72-kDa heat shock protein (HSP72), hexokinase II, and glyoxalase 1; this also enhanced insulin-stimulated Akt Ser473 phosphorylation and citrate synthase activity. However, these adaptations were suppressed with MG treatment. In the soleus muscle, the exercise-induced increases in the expression of TLR4, HSP72, and advanced glycation end products receptor 1 were inhibited with MG treatment. These findings suggest that MG is a factor that inhibits endurance exercise-induced molecular responses including mitochondrial adaptations, insulin signaling activation, and the upregulation of several proteins related to mitochondrial biogenesis, glucose handling, and glycation in primarily fast-twitch skeletal muscle.NEW & NOTEWORTHY This study investigated the effect of methylglyoxal, which is a highly reactive carbonyl metabolite and has detrimental effects on the body, on skeletal muscle adaptations following endurance exercise. Evidences from this study show that methylglyoxal is a factor deteriorating responsiveness to endurance exercise in primarily fast-twitch skeletal muscle. The findings contribute to understand the internal factors that should be focused to maximize the exercise effects.

Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP).

The somatotropic axis is required for a number of biological processes, including growth, metabolism, and aging. Due to its central effects on growth and metabolism and with respect to its positive effects on muscle mass, regulation of the GH/IGF-system during endurance exercise is of particular interest. In order to study the control of gene expression and adaptation related to physical performance, we used a non-inbred mouse model, phenotype-selected for high running performance (DUhTP). Gene expression of the GH/IGF-system and related signaling cascades were studied in the pituitary gland and muscle of sedentary males of marathon and unselected control mice. In addition, the effects of three weeks of endurance exercise were assessed in both genetic groups. In pituitary glands from DUhTP mice, reduced expression of Pou1f1 (p = 0.002) was accompanied by non-significant reductions of Gh mRNA (p = 0.066). In addition, mRNA expression of Ghsr and Sstr2 were significantly reduced in the pituitary glands from DUhTP mice (p ≤ 0.05). Central downregulation of Pou1f1 expression was accompanied by reduced serum concentrations of IGF1 and coordinated downregulation of multiple GH/IGF-signaling compounds in muscle (e.g., Ghr, Igf1, Igf1r, Igf2r, Irs1, Irs2, Akt3, Gskb, Pik3ca/b/a2, Pten, Rictor, Rptor, Tsc1, Mtor; p ≤ 0.05). In response to exercise, the expression of Igfbp3, Igfbp 4, and Igfbp 6 and Stc2 mRNA was increased in the muscle of DUhTP mice (p ≤ 0.05). Training-induced specific activation of AKT, S6K, and p38 MAPK was found in muscles from control mice but not in DUhTP mice (p ≤ 0.05), indicating a lack of mTORC1 and mTORC2 activation in marathon mice in response to physical exercise. While hormone-dependent mTORC1 and mTORC2 pathways in marathon mice were repressed, robust increases of Ragulator complex compounds (p ≤ 0.001) and elevated sirtuin 2 to 6 mRNA expression were observed in the DUhTP marathon mouse model (p ≤ 0.05). Activation of AMPK was not observed under the experimental conditions of the present study. Our results describe coordinated downregulation of the somatotropic pathway in long-term selected marathon mice (DUhTP), possibly via the pituitary gland and muscle interaction. Our results, for the first time, demonstrate that GH/IGF effects are repressed in a context of superior running performance in mice.

Effect of Endurance Exercise and MitoQ Intake on Tau Hyperphosphorylation, Oxidative Stress, Antioxidant Modulating Factors, Mitochondrial Function, and Cognitive Function in Alcl3-Induced Alzheimer’s Disease Animal Model

PURPOSE: This study aimed to investigate the effect of 8 weeks of endurance exercise and MitoQ intake on tau hyperphosphorylation, oxidative stress, antioxidant modulating factors, mitochondrial function, and cognitive function in an AlCl3-induced Alzheimer’s disease animal model.METHODS: For the experimental animals, 40 mg/kg of aluminum chloride (AlCl3) was diluted with physiological saline for 60 days and intraperitoneally injected to create an Alzheimer’s disease animal model. In addition, endurance exercise was performed at a speed of 12 m/min using a treadmill for laboratory animals for 8 weeks, and MitoQ was applied with a 100 μm concentration of negative water. The rats were randomly divided into five groups: a saline control group (NC, n=6), an AlCl3 injection group (AC, n=6), an AlCl3 injection and treadmill exercise group (AE, n=6), an AlCl3 injection and MitoQ group (AM, n=6), and an AlCl3 injection and treadmill exercise and MitoQ intake group (AEM, n=6). The SPSS program was used for statistical analyses. Differences between the groups in each variable were analyzed using the one-way ANOVA.RESULTS: Endurance exercise and MitoQ intake for 8 weeks showed positive results in cognitive function and decreased tau hyperphosphorylation in the animal model with Alzheimer’s disease. In addition, they reduced oxidative stress (4-HNE, MDA) and had a positive effect on antioxidant indicators (catalase, SOD-1, SOD-2). Finally, they exhibited a positive effect on factors related to mitochondrial function (PGC-1, Tfam).CONCLUSIONS: Eight weeks of endurance exercise and MitoQ intake are thought to have a positive effect in alleviating Alzheimer’s disease in terms of improving cognitive function through AlCl3 accumulation, tau hyperphosphorylation, oxidative stress, antioxidant modulating factors, and mitochondrial function.

Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health

ObjectivesRegular physical exercise improves health by reducing the risk of a plethora of chronic disorders. We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health. Methods and resultsBy studying changes in histone modifications, we mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary men before and after 6 weeks of endurance exercise. We identified extensive remodeling of enhancer activities after exercise training, with a large subset of the remodeled enhancers located in the proximity of genes transcriptionally regulated after exercise. By overlapping the position of enhancers with genetic variants, we identified an enrichment of disease-associated genetic variants within the exercise-remodeled enhancers. ConclusionOur data provide evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans.

Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects.

Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

Effects of Exercise Training and IL-6 Receptor Blockade on Gastric Emptying and GLP-1 Secretion in Obese Humans: Secondary Analyses From a Double Blind Randomized Clinical Trial.

BackgroundInterleukin-6 (IL-6) is released from skeletal muscle during exercise and systemic IL-6 levels therefore increase acutely in response to a single bout of exercise. We recently showed that an acute increase in IL-6 delayed gastric emptying rate and improved postprandial glycemia. Here we investigate whether repeated increases in IL-6, induced by exercise training, influence gastric emptying rate and moreover if IL-6 is required for exercise-induced adaptations in glycemic control including secretion of glucagon and glucagon-like peptide-1 (GLP-1).MethodsA total of 52 abdominally obese non-diabetic men and women were randomly assigned into four groups performing 12 weeks of endurance exercise or no exercise with or without IL-6 receptor blockade (tocilizumab). The primary endpoint was change in gastric emptying rate in response to the intervention and other endpoints included changes in glycemic control, glucagon, and GLP-1 secretion.ResultsThere was no change in gastric emptying rate in any of the four groups following the intervention and comparing differences in change between groups also revealed no difference. Postprandial glucose remained unchanged in all groups but the exercise + tocilizumab group, which improved postprandial glucose in response to the intervention. The area under the curve for meal-stimulated glucagon, active and total GLP-1 increased in response to IL-6 receptor blockade, this effect was independent of exercise.ConclusionExercise training and long-term IL-6 receptor blockade did not change gastric emptying rates in obese humans. IL-6 receptor blockade increased glucagon and GLP-1 secretion and implicate IL-6 in the regulation of the human alpha and L cells.

Adeno-Associated Virus-Mediated Knockdown of SLC16A11 Improves Glucose Tolerance and Hepatic Insulin Signaling in High Fat Diet-Fed Mice.

SLC16A11, a member of the SLC16 family, is associated with lipid metabolism, causing increased intracellular triacylglycerol (TAG) levels. In the current study, our primary goal was to determine if an SLC16A11 knockdown would improve glucose tolerance and hepatic insulin signaling in high fat diet (HFD)-fed mice. Additionally, the mechanism for exercise-improved insulin sensitivity remains unclear, and there is no mechanistic insight into SLC16A11's role in insulin sensitivity under exercise stress. Therefore, we also examined the impact of endurance exercise on the abundance of SLC16A11. C57BL/6 J male mice were fed either regular chow (Control) or HFD for 8 weeks and then injected with adeno-associated virus (AAV). Plasma parameters, tissue lipid contents, glucose tolerance, and expression profiles of hepatic insulin signaling were detected. Also, other mice were divided randomly into sedentary and exercise groups. We assessed hepatic expression of SLC16A11 after 8 weeks of endurance exercise. 1) Hepatic SLC16A11 expression was greater in HFD-fed mice compared to Control mice. 2) AAV-mediated knockdown of SLC16A11 improved glucose tolerance, prevented TAG accumulation in serum and liver, and increased phosphorylation of protein kinase B (Akt) and glycogen synthesis kinase-3β (GSK3β) in HFD-fed mice. 3) Endurance exercise decreased hepatic SLC16A11 expression. Inactivation of SLC16A11, which is robustly induced by HFD, improved glucose tolerance and hepatic insulin signaling, independent of body weight, but related to TAG. Additionally, SLC16A11 might mediate the health benefits of endurance exercise.

Exercise Training Normalizes Timing of Left Ventricular Untwist Rate, but Not Peak Untwist Rate, in Individuals with Type 2 Diabetes and Diastolic Dysfunction: A Pilot Study

There is limited information regarding the role of left ventricular (LV) twist and the effect of exercise in type 2 diabetes (T2D). The aim of this study was to compare LV twist parameters in patients with T2D versus healthy control subjects and the effects of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on LV twist in patients with T2D with diastolic dysfunction. This study, which included both prospective and retrospective components, included 47 patients with T2D and diastolic dysfunction and 37 healthy individuals. Patients with T2D were randomized to HIIE (4×4min at 90%-95% of maximal heart rate, three times a week, 120min/wk; n=24) or MIE (210min/wk; n=23) for 12weeks and examined with echocardiography (LV twist by speckle-tracking method) at baseline and posttest. The control subjects received no intervention and were matched according to age, gender, and body mass index to those completing the intervention. In total, 37 subjects completed 12weeks of MIE (n=17) or HIIE (n=20). LV peak untwist rate (UTR) was similar in patients with T2D and control subjects (P˃.05). At baseline, LV peak UTR, relative to total diastolic period, occurred 5.8 percentage points later in patients with T2D compared with control subjects (P=.004). Time to peak UTR was shortened by 6.5 percentage points (P=.002) and 7.7 percentage points (P<.001) after MIE and HIIE, respectively. Time to peak UTR was similar to that in control subjects after exercise interventions. In patients with T2D and diastolic dysfunction, LV peak UTR was similar, but time to peak LV UTR was delayed compared with control subjects. Twelve weeks of endurance exercise normalized the timing of UTR.

Influence of Endurance Exercise Overloading Patterns on the Levels of Left Ventricular Catechoamines After a Bout of Lactate Threshold Test in Male Wistar Rat.

Background:It is well known that exercise training has positive effect on catecholamine response to a given work load. But in this regard, the effective method of training needs to be studied.Objectives:The aim of this study was to compare the effects of 8 weeks endurance exercise with two overloading patterns on the left ventricular catecholamine levels.Materials and Methods:29 male Wistar rats were randomly assigned to control (n = 9), daily sinusoidal overloading (n = 10) and weekly sinusoidal overloading (n = 10) groups. After the last exercise session, left ventricular blood samples were obtained immediately after lactate threshold test. Plasma concentrations of adrenaline and noradrenaline were measured by ELISA method. One way analysis of variance was used for analysis of the data.Results:Immediately after lactate threshold test, adrenaline level was significantly (P < 0.05) lower in weekly loading group than in control and daily loading groups. Adrenaline was higher in the daily loading group compared with control group but did not reach the significant level. Noradrenaline levels were not significantly (P > 0.05) different between three study groups.Conclusions:The results showed 8 weeks of endurance exercise with weekly sinusoidal overloading pattern could induce a lower adrenal medulla activity (reflection of physical and physiological improvement) than daily sinusoidal loading pattern in response to the same absolute work load.

Similar skeletal muscle angiogenic and mitochondrial signalling following 8 weeks of endurance exercise in mice: discontinuous versus continuous training

Little is known about skeletal muscle adaptation to discontinuous endurance training. It has been suggested that accumulating 30 min of endurance exercise daily may result in similar adaptations in the working muscle to a 30 min exercise bout. The purposes of the present investigation, therefore, were to conduct an 8 week continuous or discontinuous endurance training regimen and determine the following: (i) whether treadmill exercise capacity differs between the two training regimens; and (ii) whether the angiogenic and mitochondrial signalling pathways are differentially activated in the two training regimens. Twenty-four young adult male FVB/NJ mice were randomized into the following three groups: control; continuous treadmill endurance training for 30 min five times a week; or discontinuous treadmill endurance training for a total of 30 min five times per week for three 10 min intervals with 2 h rest between intervals. After the intervention, endurance capacity increased by 60% (P < 0.001) in both exercise groups compared to control animals. For the quadriceps muscle, anti-angiogenic regulators (thrombospondin-1 and ADAMTS1) were reduced by 50-70% (P < 0.001) with either exercise regimen. In addition, phosphorylation of p38 mitogen-activated protein kinase signalling increased by 50-300% (P < 0.001), which corresponded to an increase in peroxisome proliferator-activated receptor γ coactivator 1 β (PGC-1β) protein expression. These findings suggest that accumulating 30 min of endurance exercise in 10 min sessions results in similar endurance training adaptations in skeletal muscle to a 30 min exercise bout.

Effects of Endurance Exercise on Mitochondrial Function in Mice

[Purpose] The purpose of this study was to investigate the effects of 8 weeks of endurance exercise on the cardiac mitochondrial function of mice. [Subjects] Ten 129 SvJ/C57BL6 Male mice were used. The mice were randomly divided into an exercise group (n=5; mean ± SD weight, 27.4 ± 1.6 g) and a control (n=5; mean ± SD weight, 28.2 ± 1.1 g). The exercise mice ran on a motor driven treadmill 5 days per week for 30 minutes at a speed of 24 m/min for 8 weeks. Mitochondrial function as measured RCI was compared between the exercise and control group mice using an independent t test. [Results] The exercise mice had a significantly greater state 4 respiration than to the sedentary control mice. There was also a significant difference in RCI between exercise and sedentary control mice. [Conclusion] Endurance exercise decreased RCI, indicating an uncoupling of respiration and oxidative phosphorylation.

Effect of endurance and strength exercise on release of brain natriuretic peptide

Objectives:The aim of this study was to investigate the effects of 8-week endurance and resistance exercise training on release of brain natriuretic peptide.Materials and Methods:Study population was categorized into 4 groups: Group-1 (n = 6) consisted of sedentary individuals who volunteered to complete 8-weeks of endurance exercise; Group-2 (n=6) consisted of sedentary individuals who volunteered to complete 8-weaks of resistance exercise. Three blood samples [for Terminal pro BNP (NT-Pro-BNP)] were taken before, immediately after exercise and after 8 weeks of exercise training.Results:NT-Pro BNP was significantly increased immediately after endurance exercise [from 37.9 ± 1.4 pg/ml to 52.1 ±1.5 pg/ml; P = 0.002] and was decreased to 23.2 ± 9.3 pg/ml after 8 weeks of endurance exercise [P = 0.013]. On the other hand, NT-Pro BNP showed no significant changes immediately after resistance exercise [from 26.6 ± 4.9 pg/ml to 24.1 ±4.5 pg/ml; P = 0.553]. In contrast, NT-Pro BNP was significantly increased to 39.5 ±1.6 pg/ml after 8 weeks of resistance exercise [P = 0.012].Conclusion:Endurance exercise training reduces circulating NT-Pro BNP concentration, which is likely a marker of reduced ventricular wall tension and improved myocardial function. In contrast, strength exercise induces significant increase in NT-Pro BNP, which could be partially attributed to myocardial damage.

Age-related levels of GABA/benzodiazepine binding sites in cerebrum of F-344 rats: Effects of exercise

We examined γ-aminobutyric acid (GABA), benzodiazepine and convulsant sites of postsynaptic GABA/benzodiazepine receptors (GBZR) in cerebral membranes of inbred Fischer 344 male rats as a function of age. In aged rats (23 to 24 months), the benzodiazepine binding site as determined by [ 3H]flunitrazepam was 47% and 43% lower than corresponding values in young adult (3 to 4 months) and mature (10 to 12 months) rats, respectively. The decrease was due to the loss of binding density rather than a change in affinity. No statistically significant age-related changes in [ 3H]muscimol binding were observed when 5 nM or 40 nM labeled muscimol were used. GABA produced a dose-dependent stimulation of flunitrazepam binding in all age groups, but the maximum stimulation in aged animals was significantly higher (24%) than in young and mature animals. The [ 35S]TBPS binding site, the convulsant site of GABA/benzodiazepine receptors, was unaffected with age. We also studied the effects of exercise on GBZR binding sites of aged rats. The decline of flunitrazepam binding sites and the high sensitivity of flunitrazepam binding to regulation by GABA in aged animals were reversed by 8 to 10 weeks of endurance exercise. Endurance exercise did not have any significant effect on muscimol or TMPS binding sites. Results suggest that there are aged-related alterations of GBZR binding sites and that these modifications can be reversed by exercise.

Chronic exercise produces tolerance to muscarinic antagonists in rats

Previous work has shown that exercise can modify behavioral sensitivity to antimuscarinic compounds. The present study examined the effct of 10 weeks of endurance exercise on atropine and scopolamine potency. The behaviorally disruptive effects of these compounds were evaluated in rats trained to respond under a MULT TO FR30 schedule of reinforcement for food reward. Following 10 weeks of endurance exercise, atropine and scopolamine dose response curves were significantly altered. The ED50 values were increased 10 and 40-fold, respectively. Tolerance to atropine or scopolamine has been reported previously only in response to chronic drug administration. The present data demonstrate that non-drug factors can significantly influence behavioral response to muscarinic antagonists.