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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5-HT levels to a minimum of 73.0 +/- 3.5% of baseline after the first injection (P < 0.01) and to 68.5 +/- 5.5% of baseline after the second injection (P < 0.01) and consequently prevented the exercise-induced 5-HT enhanced levels. We have observed the same phenomenon concerning the 5-HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise-induced increase of 5-HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5-HT, but probably on the release/reuptake system.
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PMID:Evidence that brain glucose availability influences exercise-enhanced extracellular 5-HT level in hippocampus: a microdialysis study in exercising rats. 1219 20

Paeonia radix is the root of Paeonia japonica MIYABE, a perennial plant classified in the family Paeoniaceae. In the present study, the effects of Paeonia radix on performance in treadmill exercise, and 5-hydroxytryptamine (5-HT) synthesis and tryptophan hydroxylase (TPH) expression in the dorsal raphe were investigated. Time to exhaustion in treadmill exercise was increased and exercise-induced increases in 5-HT synthesis and TPH expression in the dorsal raphe were shown to be suppressed by Paeonia radix treatment; 5-HT synthesis and TPH expression were inhibited by Paeonia radix treatment under resting conditions as well. In sum, treatment with Paeonia radix, inhibiting 5-HT synthesis and TPH expression, may bring about reduced fatigue, both during exercise and the resting state.
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PMID:Effects of Paeonia radix on 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of exercised rats. 1257 75

We have studied 12 recreationally active men to measure their responses to exercise in the heat and relate these to measures of hypothalamic function explored with a buspirone [5-hydroxytryptamine 1A (5-HT(1A)) agonist, dopaminergic D(2) antagonist] neuroendocrine challenge, with and without pretreatment with pindolol (5-HT(1A) antagonist). Pindolol treatment allowed the serotonergic and non-serotonergic components of prolactin release to be distinguished. Subjects exercised at 73 (5)% maximal rate of oxygen uptake (VO(2max)) until volitional fatigue at 35 degrees C (relative humidity, 30%). On another two occasions they underwent a buspirone challenge [0.5 mg (kg body mass)(-1)], once with, and once without, pindolol [0.5 mg (kg body mass)(-1)] pretreatment and the circulating plasma concentrations of prolactin were measured for the next 2.5 h. Rectal temperature increased throughout exercise, whilst mean skin temperature remained constant. There was a wide inter-subject variation in prolactin response to the neuroendocrine challenges. The proportion of the prolactin response to buspirone attributable to a non-serotonergic component (most likely dopaminergic) correlated both with exercise duration (r=0.657, P=0.028), rectal temperature at fatigue (r=0.623, P=0.041) and the rate of temperature rise (r=-0.669, P=0.024). Our results suggest that high activity of the dopaminergic pathways in the hypothalamus is a predictor of exercise tolerance in the heat.
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PMID:Responses to exercise in the heat related to measures of hypothalamic serotonergic and dopaminergic function. 1268 6

Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery. Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake and ratings of perceived exertion were measured at rest, and during exercise and recovery. Peak oxygen uptake was significantly lower in the CFS patients compared with controls. Rating of perceived exertion in the patients was higher at all time points measured, including at rest, relative to controls. Levels of free tryptophan (free Trp), the rate-limiting 5-HT precursor, were significantly higher in CFS patients at exhaustion and during recovery, whereas concentrations of branched-chain amino acids (BCAA) and large neutral amino acids (LNAA) were lower in CFS patients at exhaustion, and for LNAA also during recovery. Consequently, the [free Trp]/[BCAA] and [free Trp]/[LNAA] ratios were significantly higher in CFS patients, except at rest. On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the CFS patients. The significant differences observed in a number of key putative CNS 5-HT and dopaminergic modulators, coupled with the exacerbated perception of effort, provide further evidence for a potentially significant role for CNS mechanisms in the pathogenesis of CFS.
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PMID:Chronic fatigue syndrome: new evidence for a central fatigue disorder. 1270 66

Serotonin (5-hydroxytryptamine, 5-HT)-containing neurons in the midbrain directly innervate corticotropin-releasing hormone (CRH)-containing cells located in paraventricular nucleus of the hypothalamus. Serotonergic inputs into the paraventricular nucleus mediate the release of CRH, leading to the release of adrenocorticotropin, which triggers glucocorticoid secretion from the adrenal cortex. 5-HT1A and 5-HT2A receptors are the main receptors mediating the serotonergic stimulation of the hypothalamic-pituitary-adrenal axis. In turn, both CRH and glucocorticoids have multiple and complex effects on the serotonergic neurons. Therefore, these two systems are interwoven and communicate closely. The intimate relationship between serotonin and the hypothalamic-pituitary-adrenal axis is of great importance in normal physiology such as circadian rhythm and stress, as well as pathophysiological disorders such as depression, anxiety, eating disorders, and chronic fatigue.
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PMID:Serotonin and the neuroendocrine regulation of the hypothalamic--pituitary-adrenal axis in health and disease. 1285 56

The introduction of substance P into the lumen of the isolated guinea-pig ileum caused an increase in the number and amplitude of the peristaltic waves. In preparations in which the peristaltic reflex was abolished, by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath, the introduction of substance P into the lumen of the intestine restored peristalsis. This effect of substance P was absent in preparations in which the mucous membrane was removed. Hexamethonium abolished the effect of substance P on peristalsis. It is concluded that substance P acts on the afferent nervous elements of the peristaltic reflex arc, possibly on the sensory receptors.
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PMID:The effect of substance P on the peristaltic reflex of the isolated guinea-pig ileum. 1358 37

To establish an animal model of fatigue, we kept rats in a cage filled with water to a height of 1.5 cm. We selected a weight-loaded forced swimming test for evaluation of the extent of fatigue. Animals kept in the wet cage for 5 days showed a reduction in 2-[18F]fluoro-2-deoxy-D-glucose uptake into their brain. The session for 1 day showed significantly increased 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) and [3,4-dihydroxyphenyl-acetic acid (DOPAC)+homovanillic acid (HVA)]/dopamine (DA) ratios in all brain regions, but the session for 5 days showed the restoration of the 5-HIAA/5-HT ratio in the hippocampus and hypothalamus and in the (DOPAC+HVA)/DA ratio in the striatum and hypothalamus. Our data suggest that decreased glucose uptake and insufficient serotonin and dopamine turnover introduced by deprivation of rest were correlated with central fatigue.
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PMID:Establishment and assessment of a rat model of fatigue. 1462 9

We recently established an animal model of fatigue in which rats were kept in a cage filled with water to a height of 1.5 cm for 5 days. In this way, after the fatigue session, they were returned to their home cage. Rats resting for 15 min or 2 h showed reduced 2-[18F]fluoro-2-deoxy-D-glucose uptake in their brain. Rats resting for 1 h showed a significantly increased ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine, an index of serotonin turnover, in the frontal cortex, hippocampus, and cerebellum, and the ratio of [3,4-dihydroxyphenylacetic acid+homovanillic acid]/dopamine, an index of dopamine turnover, tended to be increased as compared with the control. These data suggest that improvement of glucose uptake and increased serotonergic and dopaminergic neuronal activities are associated with recovery from central fatigue.
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PMID:Recovery from fatigue: changes in local brain 2-[18F]fluoro-2-deoxy-D-glucose utilization measured by autoradiography and in brain monoamine levels of rat. 1466 8

The level of tryptophan and 5-hydroxyindoleacetic acid were measured in the brain (striatum) of rats on tryptophan-deficient diet and tryptophan-enriched diet. We measured concentrations of tryptophan and 5-hydroxyindoleacetic acid in striatum by using microdialysis and HPLC methods. The extracellular level of tryptophan and 5-hydroxyindoleacetic acid concentration in the striatum of a tryptophan-reduced rats was decreased by about 50% compared with a tryptophan-enriched diet. In the tryptophan-reduced condition, the rats an increased the running time of more than 100 min, compared with those on a tryptophan-enriched diet. These results suggest the tryptophan and 5-hydroxytryptamine in the central nervous system are involved in fatigue.
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PMID:The effect of tryptophan deficiency in the brain on rat fatigue levels: a rat model of fatigue reduction. 1520 70

Almotriptan (LAS 31416) is a new, oral, specific 5-hydroxytryptamine(1B/1D) receptor agonist for the treatment of migraine. The pharmacokinetics and safety of a range of oral doses were assessed in 23 healthy male volunteers. Peak plasma concentrations were reached between 1.5 and 4 h after dosing. The maximum plasma concentration and area under the curve showed dose proportionality over the dose range 5-200 mg. The elimination half-life was constant at approximately 3 h across all dose levels. A substantial proportion of the initial dose was excreted in urine (27%-39%) during 12 h post-dose and the main excretory product was unchanged drug. Three major urinary metabolites were detected, all of which were pharmacologically inactive. The most common events following almotriptan administration were headache, tiredness and mild nausea. Nine events (18%) were classed as probably related to almotriptan and these were all at the highest dose level of 200 mg. The maximum tolerated dose of almotriptan was, therefore, determined as 150 mg. In conclusion, almotriptan is well tolerated following single, oral doses up to 150 mg and has predictable pharmacokinetics.
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PMID:Pharmacokinetics and safety of oral almotriptan in healthy male volunteers. 1538 81


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