Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems.

Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling that leads to reduced intensity or interruption of physical exercises, thereby regulating performance. The present review aims to present advances on the understanding of fatigue, which has recently been proposed as a defense mechanism instead of a "physiological failure" in the context of prolonged (aerobic) exercises. We also present recent advances on the association between serotonin, dopamine and fatigue. Experiments with rodents, which allow direct manipulation of brain serotonin and dopamine during exercise, clearly indicate that increased serotoninergic activity reduces performance, while increased dopaminergic activity is associated with increased performance. Nevertheless, experiments with humans, particularly those involving nutritional supplementation or pharmacological manipulations, have yielded conflicting results on the relationship between serotonin, dopamine and fatigue. The only clear and reproducible effect observed in humans is increased performance in hot environments after treatment with inhibitors of dopamine reuptake. Because the serotonergic and dopaminergic systems interact with each other, the serotonin-to-dopamine ratio seems to be more relevant for determining fatigue than analyzing or manipulating only one of the two transmitters. Finally, physical training protocols induce neuroplasticity, thus modulating the action of these neurotransmitters in order to improve physical performance.

Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C) followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure.

Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C) followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

Intrinsic exercise capacity is related to differential monoaminergic activity in the rat forebrain.

Monoamines levels in central nervous system have been associated with exercise performance and fatigue. The present study investigated whether intrinsic exercise capacity is associated with differential activity of monoamines in the caudate-putamen (CPu) and accumbens (ACC) nucleus. Male Wistar rats were subjected to a progressive testing protocol. Based on the maximal time of exercise in the progressive testing protocol (TEPmax), the animals were divided into low-performance (LP), high-performance (HP), and standard-performance (SP) groups. After classification, eight animals in each group were chosen randomly and evaluated in two experimental situations: rest (n=8) or moderate exercise (ME) at 60% of maximal velocity (n=8). The CPu and ACC were dissected for analyses of monoamine levels. At rest, HP rats exhibited higher 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio and lower serotonin (5-HT) concentration compared other groups, and lower 5-hydroxyindoleacetic (5-HIAA) compared with the LP rats. The ME resulted in increased DOPAC/DA ratio in the CPu of all experimental groups. In both the CPu and ACC, ME increased 5-HIAA levels in SP and HP rats and 5-HIAA/5-HT ratio only in HP rats. Thus, our findings demonstrate that rats with natural intrinsic differences in performance to exercise exhibit alterations in dopaminergic and serotonergic systems at rest and after ME exercise until fatigue.

Effect of a physical exercise program on the functional capacity of liver transplant patients.

BACKGROUND: Recently there has been great concern about the quality of life and health of liver transplant patients (LTP). These patients often present with metabolic disorders, which can improve with regular physical exercise. The aim of this study was to investigate the effect of a physical exercise program on the functional capacity of LTP. METHOD: The distance walked in the 6-minute walk test and the resting energy expenditure (REE) were evaluated in 15 subjects who regularly attend the outpatient Bias Fortes Clinic at Universidade Federal de Minas Gerais. The patients were divided into 2 groups, the Exercise Group (EG) (6 men and 3 women; 52 ± 15 years old, BMI 22.4 ± 4.0 kg/m²) performed 24 sessions of continuous 30 min treadmill exercise. Intensity of exercise was increased from 50%-70% of the maximum heart rate over the training period. A group of 3 men and 3 women (39 ± 15 years, BMI 24.5 ± 4.4 kg/m²) served as controls (CG). RESULTS: After undergoing exercise training, patients in the EG showed a 19.4% increase in the distance walked (pre = 453.6 ± 128.0 m and post = 582.5 ± 90.1 m). Also, there was an increase in their REE (pre = 1,060.0 ± 194.2 kcal and post = 1,375.0 ± 258.6 kcal) (P < .05) indicating an increase in their exercise capacity and metabolic improvements. There were no differences in the distance walked (pre = 516.5 ± 62.0 m and post = 517.7 ± 71.9 m) and REE (pre = 1,393.0 ± 213.3 kcal to post = 1,465.0 ± 170.3 kcal) (P > .05) for CG. Our results are in agreement with previous studies. CONCLUSIONS: We conclude that the exercise program promoted significant improvements in functional capacity. These findings have positive implications for the control of metabolic diseases, which are common in patients after liver transplantation.

Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats.

Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p-CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p-CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 µM) and underwent a submaximal exercise test until fatigue. Icv TRP-treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p-CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p-CPA administration accelerated cutaneous heat dissipation when compared with saline-pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p-CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.

Competition, estimated, and test maximum heart rate.

AIM: The aim of the present study was to compare the highest heart rate (HR) of soccer players recorded during competition matches with the maximum HR (HR(max)) estimated from age and the highest HR recorded in effort tests within a single category (intracategory) and between categories (intercategories). METHODS: The sample was made up of 19 under-17 athletes, 12 under-20 athletes and 14 professional athletes of a Brazilian first division soccer team. Players' HR was monitored during official competition matches and maximum effort test with a set of HR monitors. The highest HR recorded during competitive matches (MHR1) was considered as the highest HR value attained by each player during matches. HR(max) estimated from age (MHR2) was estimated by using the equation HR(max)= (220-age). The highest HR recorded in effort tests (MHR3) was determined as being the highest HR value recorded during a maximum effort test (1 000-m run). The Wilcoxon test was used in intracategory statistical analysis. The Kruskal Wallis test was used in intercategory statistical analysis. The significance level adopted was P<0.05. RESULTS: In all categories, MHR3 was lower than MHR1. Concerning intercategory analysis, the three categories did not exhibit a difference in MHR1 RESULTS: Relative to MHR3, the under-17 and under-20 categories were not different from each other. These two categories exhibited larger MHR3 values than the professional one did. CONCLUSION: HR(max) measured during field tests can be underestimated in relation to that measured during competition activities, maybe because the tests represent an artificial situation for athletes, who do not feel as motivated as during competitions.

Intracerebroventricular tryptophan increases heating and heat storage rate in exercising rats.

The role of increased hypothalamic tryptophan (TRP) availability on thermoregulation and rates of core temperature increase and heat storage (HS) during exercise was studied in normal untrained rats running until fatigue. The rats were each anesthetized with 2.5% tribromoethanol (1.0 ml kg(-1) ip) and fitted with a chronic guiding cannula attached to the right lateral cerebral ventricle 1 week prior to the experiments. Immediately before exercise, they were randomly injected through these cannulae with 2.0 microl of 0.15 M NaCl (SAL; n=6) or 20.3 microM L-TRP solution (n=7). Exercise consisted of running on a treadmill at 18 m min(-1) and 5% inclination until fatigue. Body temperature was recorded before and during exercise with a thermistor probe implanted into the peritoneal area. Rates of core temperature increase (HR, degrees C min(-1)) and heat storage (HSR, cal min(-1)) were calculated. TRP-treated rats showed a rapid increase in body temperature which was faster than that observed in the saline-treated group during the exercise period. The TRP group also showed a higher rate of core temperature increase and HS. TRP-treated rats that presented higher HR and HSR also fatigued much earlier than saline-treated animals (16.8+/-1.1 min TRP vs. 40+/-3 min SAL). This suggests that the reduced running performance observed in TRP-treated rats is related to increased HR and HSR induced by intracerebroventricular injection of TRP in these animals.

Evidence that tryptophan reduces mechanical efficiency and running performance in rats.

It has been reported that exercise increases brain tryptophan (TRP), which is related to exhaustive fatigue. To study this further, the effect of increased TRP availability on the central nervous system (CNS) with regard to mechanical efficiency, oxygen consumption (VO(2)) and run-time to exhaustion was studied in normal untrained rats. Each rat was anesthetized with thiopental (30 mg/kg ip b. wt.) and fitted with a chronic guiding cannula attached to the right lateral cerebral ventricle 1 week prior to the experiments. Immediately before exercise, the rats were randomly injected through these cannulae with 2.0 microl of 0.15 M NaCl (n=6) or 20.3 microM L-TRP solution (n=6). Exercise consisted of running on a treadmill at 18 m min(-1) and 5% inclination until exhaustion. TRP-treated rats presented a decrease in their mechanical efficiency (21.25+/-0.84%, TRP group vs. 24.31+/-0.98%, saline-treated group; P< or =.05), and increased VO(2) at exhaustion (40.3+/-1.6 ml kg(-1) min(-1), TRP group vs. 36.0+/-0.8 ml kg(-1) min(-1), saline group; P< or =.05), indicating that the metabolic cost of exercise was higher in the former group. In addition, a highly significant reduction was also observed in run-time to exhaustion of TRP animals compared to those of the saline-treated group (15.2+/-1.52 min, TRP group vs. 50.6+/-5.4 min, saline group; P< or =.0001). It can be deduced from the data that intracerebroventricular TRP injection in rats increases O(2) consumption and reduces mechanical efficiency during exercise, diminishing running performance.

Effects of caffeine on the rate of perceived exertion.

The role of caffeine in improving performance in endurance exercises is controversial and its mechanism of action is not well understood. The purpose of the present study was to evaluate the effects of caffeine on the rate of perceived exertion (RPE) by exercising athletes. Six male non-smoking runners, aged 26.8 +/- 4.9 years (mean +/- SD), who had been in training continuously for at least two years before the experiment were studied. Mean maximum oxygen consumption (VO2max) was 61.21 +/- 5.36 ml kg-1 min-1. The subjects were asked to exercise on a bicycle ergometer for 3 min each at 300 and 600 kg m min-1, after which the work load was elevated to 1200 kg m min-1 and they exercised until exhaustion. In order to evaluate the effects of caffeine, the exercise was performed twice following the ingestion of 200 ml decaffeinated coffee with and without caffeine (5 mg/kg body weight). Caffeine had no significant effect on exercise time, pulmonary ventilation, oxygen consumption, carbon dioxide extraction or exchange respiratory ratio, but the RPE was significantly lower (P less than 0.05) at the work load of 1200 kg m min-1 after the ingestion of caffeine for both trials I and II. The present results suggest that metabolic acidosis and glycogen depletion were not the main causes of exhaustion.

Effects of caffeine on the rate of perceived exertion

The role of caffeine in improving performance in endurance exercises is controversial and its mechanism of action is not well understood. The purpose of the present study was to evaluate the effects of caffeine on the rate of perceived exertion (RPE) by exercising athletes. Six male non-smoking runners, aged 26.8 ñ 4.9 years (mean ñ SD), who had been in training continuously for at least two years before the experiment were studied. Mean maximum oxygen consumption (VO2max) was 61.21 ñ 5.36 ml kg**-1 min**-1. The subjects were asked to exercise on a bicycle ergometer for 3 min each at 300 and 600 kg m min**-1, after which the work load was elevated to 1200 kg m min**-1 and they exercised until exhaustion. In order to evaluate the effects of caffeine, the exercicse was performed twice following the ingestion of 200 ml decaffeinated coffee with and without caffeine (5 mg/kg body veight). Caffeine had no significant effect on exercise time, pulmonary ventilation, oxygen consumption, carbon dioxide extraction or exchange respiratory ratio, but the RPE was significantly lower (P<0.05) at the work load of 1200 kg m min**-1 after the ingestion of caffeine for both trials I and II. The present results suggest that metabolic acidosis and glycogen depletion were not the main causes of exhaustion