Beneficial Effects of Photoperiod Lengthening on Sleep Characteristics and Mechanical Hyperalgesia in Injured Rats.

Sleep and muscle injury-related pain are in negative relationship, and sleep extension may be a favorable countermeasure. In response to muscle injury, an adaptive sleep response has been described in rats, characterized by an increase in total sleep time (TST) and nonrapid eye movement (NREM) sleep. This study examined the effects of photoperiod lengthening (a model of sleep prolongation in rats) on the sleep characteristics of muscle-injured rats and whether this lengthening could benefit injury-induced mechanical hyperalgesia using the Von Frey test. Switching from the conventional 12:12 light/dark (LD) photoperiod (light on: 08:00-20:00) to LD 16:8 (light extended to 24:00) gives rats an extra window of sleep. Our results show higher TST and NREM sleep times in LD 16:8 versus LD 12:12 injured rats during 4 h of light lengthening for 7 d postinjury, showing the efficiency of photoperiod lengthening to increase sleep time in injured rats. In addition, a cumulative effect with the adaptive sleep response to muscle injury occurred with higher TST and NREM sleep times in LD 16:8 injured versus noninjured rats during the dark period, reflecting the high need for sleep after the injury. Greater stability and higher relative delta power of NREM sleep during the extended light period were also observed in injured rats. Finally, the extended photoperiod limits the muscle injury-induced mechanical hyperalgesia for 13 d and allows faster recovery of the baseline mechanical threshold. This is associated with reduced pro-inflammatory cytokines levels in the hippocampus, a brain structure involved in pain processing.

Evaluation of sleep and therapeutic education needs of military with PTSD.

Sleep disorders in post-traumatic stress disorder (PTSD) are both diagnostic (nocturnal reliving) and prognostic. Poor sleep worsens the daytime symptomatology of PTSD and makes it resistant to treatment. However, no specific treatment is codified in France to treat these sleep disorders although sleep therapies (cognitive behavioural therapy for insomnia, psychoeducation and relaxation) have proven for years to be effective in treating insomnia. Therapeutic sessions can be part of a therapeutic patient education program, which is a model for the management of chronic pathologies. It allows for an improvement in a patient's quality of life and enhanced medication compliance. We therefore carried out an inventory of sleep disorders of patients with PTSD. First, we collected data by means of sleep diaries concerning the population's sleep disorders at home. Then we assessed the population's expectations and needs regarding its management of sleep, thanks to a semi-qualitative interview. The data from sleep diaries, which was consistent with the literature, showed that our patients suffered from severe sleep disorders that strongly impact their daily lives, with 87% of patients having an increased sleep onset latency, and 88% having nightmares. We observed a strong demand from patients for specific support for these symptoms, 91% expressing an interest in a TPE program targeting sleep disorders. Thanks to the data collected, the emerging themes for a future therapeutic patient education program targeting sleep disorders of soldiers with PTSD are: sleep hygiene; management of nocturnal awakenings, including nightmares; and psychotropic drugs.

Muscle injury induces an increase in total and non-rapid eye movement sleep time.

STUDY OBJECTIVES: This study describes macro- and micro-sleep responses to a myotoxic skeletal muscle injury and investigates possible mechanisms. METHODS: We recorded the electroencephalogram (EEG)/electromyogram (EMG) of 24 Wistar rats before and after induction of tibialis anterior muscle injury (n = 8 per group: control, control + buprenorphine and injured). A top-down analysis of sleep characteristics was processed from total sleep time (TST), sleep stages, sleep stability, spectral analysis, and spindles. To further investigate the mechanisms involved, we analyzed the protein level of sleep regulatory molecules including tumor necrosis factor- α (TNF-α), interleukin-1ß (IL-1ß), insulin-like growth factor-1 (IGF-1), and brain and muscle ARNT-like 1 (BMAL1) in plasma, frontal cortex, hippocampus, and tibialis anterior, collected at day +2 after injury from non-EEG/EMG implanted rats. RESULTS: Muscle injury induces a significant increase in TST at 48 and 72 h post-injury, specific to non-rapid eye movement (NREM) sleep. These increases occur during the dark period and are associated with the higher stability of sleep over 24 h, without change in the different power/frequency spectral bands of NREM/REM sleep. There was no corresponding sleep increase in slow-wave activity or spindle density, nor were there changes in brain levels of the sleep-regulating proinflammatory cytokine IL-1ß, which is otherwise involved in the local response to injury. Conversely, decreased protein levels of brain IGF-1 and muscle BMAL1, a core circadian clock gene, after injury may play a role in increased sleep time. CONCLUSION: Muscle injury induces an increase in total sleep time at 48- and 72-h post-injury, specific to NREM sleep during the dark period in rats and is associated with higher sleep stability over 24 h.

Clinical description of sleep and trauma-related nightmares in a population of French active-duty members and veterans with Post-Traumatic Stress Disorder.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a major public health problem. The most frequent complaints in this pathology are sleep disorders and trauma-related nightmares in particular. Trauma-related nightmares are characteristic of PTSD and impact its severity insofar as they are associated with more severe, longer-lasting symptoms and resistance to first-line treatments. There are specific characteristics associated with military personnel, including overrepresentation of replicative trauma-related nightmares. The aim of this study was to provide an accurate description of sleep patterns and the characteristics of trauma-related nightmares in a population of active-duty members or veterans diagnosed with PTSD. METHODS: We recruited active-duty service members and veterans receiving treatment for PTSD in the psychiatric departments of five Military Teaching Hospitals (Hôpitaux d'Instruction des Armées, HIA) and described their sleep characteristics using a questionnaire, the Trauma-Related Nightmare Survey French version (TRNS-FR). RESULTS: Out of 77 patients, 72 (93.5%) who experienced traumatic nightmares were included. This population had very severe clinical manifestations of PTSD, with a mean PCL-S score of 62.6 and an estimated total sleep time of 5.3h (317min). Among these patients, 31% had replicative nightmares and 57.7% had partially replicative nightmares. Nightmares were frequent (4.7 nightmares on average over the previous week), highly realistic, and highly immersive with exacerbated symptoms during the nightmare and also upon awakening. DISCUSSION: Sleep quality was seriously altered among active-duty service members and veterans treated in Military Hospitals for PTSD with trauma-related nightmares. Certain criteria were identified to help characterize trauma-related nightmares: their level of replication, recurrence and the impact of these symptoms on patients' lives. CONCLUSION: Long-term traumatic nightmares are a prominent feature in the symptomatology of active service members and veterans suffering from PTSD. This symptom is of particular interest as it may be a sign of changes in the patient's condition and a potential therapeutic target.

Motorcycling performance and sleepiness during an extended ride on a dynamic simulator: relationship with stress biomarkers.

OBJECTIVE: Powered two-wheelers (PTW) make up a large proportion of fatal accidents. The aim of this study was to investigate the effects of time-of-day and total sleep deprivation (SD) on simulated motorcycling performance during extended riding sessions (60 min), while evaluating stress mechanisms. APPROACH: A total of 16 healthy males participated in four simulated motorcycling sessions at 07:00, 11:00, 15:00 and 19:00, including city (8 min), country (2 min) and highway pathways (40 min), after a normal night of sleep and after total SD (30 h), in a randomized counterbalanced order. The recorded motorcycle parameters included: variation of lateral position, number of inappropriate line crossings (ILC), falls, riding errors, speed and speed limit violations. Subject parameters included the number of microsleeps in each pathway, the number of lapses during the 3-min psychomotor vigilance task (PVT-Brief version), and the Karolinska sleepiness scale (KSS) score. Saliva samples were used to assess cortisol (sC), α-amylase (sAA), and chromogranin-A (sCgA). ANOVAs and Pearson's correlation analysis were performed between these variables. MAIN RESULTS: Most parameters were influenced by an interaction effect between 'Motorcycling pathways' × 'SD' (speed (p < 0.05), legal speed violations (p < 0.01), variation of lateral position (p < 0.001), falls (p < 0.001), EEG-microsleeps (p < 005)). An interaction effect between 'SD' × 'Time-of-day' influenced the number of ILCs (p < 0.01), sC (p < 0.05) and sCgA (p < 0.05) levels. SD affected KSS scores (p < 0.001) and PVT lapses (p < 0.05). The highest disturbances were associated with highway motorcycling simulation. SIGNIFICANCE: Sleepiness due to circadian or SD and fatigue effects significantly affect riding and increase the risks involved with PTWs. The activation of both stress systems seems not sufficient to alleviate these deleterious effects.

Effect of Sleep Extension on the Subsequent Testosterone, Cortisol and Prolactin Responses to Total Sleep Deprivation and Recovery.

Total sleep deprivation (TSD) in humans is associated with altered hormonal levels, which may have clinical relevance. Less is known about the effect of an extended sleep period before TSD on these hormonal changes. Fourteen subjects participated in two experimental counterbalanced conditions (randomised cross-over design): extended sleep (21.00-07.00 h time in bed, EXT) and habitual sleep (22.30-07.00 h time in bed, HAB). For each condition, subjects performed two consecutive phases: six nights of either EXT or HAB. These nights were followed by 3 days in the sleep laboratory with blood sampling at 07.00 and 17.00 h at baseline (B-07.00 and B-17.00), after 24 and 34 h of continuous awakening (24 h-CA, 34 h-CA) and after one night of recovery sleep (R-07.00 and R-17.00) to assess testosterone, cortisol, prolactin and catecholamines concentrations. At 24 h of awakening, testosterone, cortisol and prolactin concentrations were significantly lower compared to B-07.00 and recovered basal levels after recovery sleep at R-07.00 (P < 0.001 for all). However, no change was observed at 34 h of awakening compared to B-17.00. No effect of sleep extension was observed on testosterone, cortisol and catecholamines concentrations at 24 and 34 h of awakening. However, prolactin concentration was significantly lower in EXT at B-07.00 and R-07.00 compared to HAB (P < 0.05, P < 0.001, respectively). In conclusion, 24 h of awakening inhibited gonadal and adrenal responses in healthy young subjects and this was not observed at 34 h of awakening. Six nights of sleep extension is not sufficient to limit decreased concentrations of testosterone and cortisol at 24 h of awakening but may have an impact on prolactin concentration.

Weight Loss, Performance and Psychological Related States in High-level Weightlifters.

We examined the effects of a rapid weight loss on dietary intakes, psychological parameters and physical performance of 11 international weightlifters. During the first period (T1), all subjects maintained their body weight and participated in a simulated weightlifting competition. Then, they were assigned into 2 groups depending on whether they lost (Group 2) or maintained (Group 1) their body weight over 6 days. A battery of tests was performed at T1 and after a 6-day food restriction (T2), including assessment for body composition, performance, evaluation of mood states and fatigue. Dietary data were collected using a 6-day diet record. A 4.34% reduction of body weight was achieved by a significant reduction of total energy intakes (- 40%), inducing a significant alteration of the general recovery score (p<0.05) and evaluated through the Recovery-Stress Questionnaire for Athletes. Increase in conflicts/pressure, emotional stress and physical complaints were observed. Intakes of vitamins B1, B3, B6, B9 and magnesium were significantly lower than the recommendations during the weight loss period. However, the food restriction did not impair weightlifting performance. Reduced energy and micronutrient intakes, inducing a rapid weight loss, could be a limiting factor to training adaptations and a threat towards athlete's health if frequently used.

Effects of exercise on brain and peripheral inflammatory biomarkers induced by total sleep deprivation in rats.

BACKGROUND: Physical exercise induces neuroprotection through anti-inflammatory effects and total sleep deprivation is reported an inflammatory process. We examined whether 7 weeks of exercise training attenuates markers of inflammation during total sleep deprivation (24-h wakefulness) in the rat brain and periphery. METHODS: Four groups of 10 rats were investigated: Sedentary control, Sedentary sleep-deprived, Exercised control, and Exercised sleep-deprived. Sleep deprivation and exercise training were induced using slowly rotating wheels and a motorized treadmill. We examined mRNA expression of pro-inflammatory (IL-1ß, TNF-α, and IL-6) cytokine-related genes using real-time PCR, and protein levels in the hippocampus and frontal cortex, as well as circulating concentrations. RESULTS: Compared to Sedentary control rats, hippocampal and cortical IL-1ß mRNA expressions in Sedentary sleep-deprived rats were up-regulated (p < 0.05 and p < 0.01 respectively). At the protein level, hippocampal IL-1ß and TNF-α and cortical IL-6 contents were higher in Sedentary sleep-deprived rats (p < 0.001, p < 0.05, p < 0.05, respectively). Peripherally, TNF-α, IL-6 and norepinephrine concentrations were higher in Sedentary sleep-deprived rats compared to Sedentary control (p < 0.01, p < 0.001, p < 0.01, respectively). Exercise training reduced the sleep deprivation-induced hippocampal IL-1ß increases (mRNA expression and protein content) (p < 0.05 and p < 0.001), and TNF-α content (p < 0.001). At the periphery, exercise reduced sleep deprivation-induced increase of IL-6 concentration (p < 0.05) without effect on TNF-α and norepinephrine. CONCLUSIONS: We demonstrate that a 7-week exercise training program before acute total sleep deprivation prevents pro-inflammatory responses in the rat hippocampus, particularly the IL-1ß cytokine at the gene expression level and protein content.

In-flight automatic detection of vigilance states using a single EEG channel.

Sleepiness and fatigue can reach particularly high levels during long-haul overnight flights. Under these conditions, voluntary or even involuntary sleep periods may occur, increasing the risk of accidents. The aim of this study was to assess the performance of an in-flight automatic detection system of low-vigilance states using a single electroencephalogram channel. Fourteen healthy pilots voluntarily wore a miniaturized brain electrical activity recording device during long-haul flights ( 10 ±2.0 h, Atlantic 2 and Falcon 50 M, French naval aviation). No subject was disturbed by the equipment. Seven pilots experienced at least a period of voluntary ( 26.8 ±8.0 min, n = 4) or involuntary sleep (N1 sleep stage, 26.6 ±18.7 s, n = 7) during the flight. Automatic classification (wake/sleep) by the algorithm was made for 10-s epochs (O1-M2 or C3-M2 channel), based on comparison of means to detect changes in α, ß, and θ relative power, or ratio [( α+θ)/ß], or fuzzy logic fusion (α, ß). Pertinence and prognostic of the algorithm were determined using epoch-by-epoch comparison with visual-scoring (two blinded readers, AASM rules). The best concordance between automatic detection and visual-scoring was observed within the O1-M2 channel, using the ratio [( α+θ )/ß] ( 98.3 ±4.1% of good detection, K = 0.94 ±0.07, with a 0.04 ±0.04 false positive rate and a 0.87 ±0.10 true positive rate). Our results confirm the efficiency of a miniaturized single electroencephalographic channel recording device, associated with an automatic detection algorithm, in order to detect low-vigilance states during real flights.

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men.

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances. To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29±3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P<0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.

Influence of protein- versus carbohydrate-enriched feedings on physiological responses during an ultraendurance climbing race.

This study investigated effects of a high protein (PROT) versus a high carbohydrate (CHO) diet on performance and physiological responses during an ultraendurance climbing race at moderate altitude. On two different periods, in a randomised crossover design, ten climbers (30.0+/-0.9 years) participated in the race (duration 29 h approximately, energy expenditure 43.6+/-1.2 MJ.day (-1)) and were fed either with the PROT (30% protein content) or the CHO diet (68% carbohydrate) each providing 16.74 MJ. Mental performance was assessed by the Stroop test and we estimated maximal voluntary strength of quadriceps muscle. We quantified metabolic and hormonal circulating concentrations. Mental performance was unaffected after the two races, while muscular performance and body weight were decreased (both p<0.01) with no diet effects. Decreases were measured for IGF-I concentration and its binding protein IGFBP-3 (p<0.001), and increases for cortisol and norepinephrine (p<0.01) with no diet effects. Glucose concentration decreased (p<0.05) without diet effects, while amino acids (leucine, isoleucine, valine, and tyrosine) decreased in CHO group (p<0.001). Leptin concentration decreased (p<0.001) without diet effects, whereas total ghrelin increased in CHO group (p<0.01). Our results showed that a high PROT or high CHO intake during physical exertion at moderate altitude maintained mental performance, but did not limit muscle force reduction and body weight loss. There was decreased glucose availability, and hormonal responses indicated both catabolism and extreme energy deficiency induced by exercise with opposite responses of ghrelin and leptin. The ghrelin response was additionally indicative of macronutrient intake during the race.

Relationships between leptin levels and carbohydrate intake during rowing training.

AIM: This study was designed to determine the relationship between diet and leptin levels during rowing training. METHODS: Dietary intakes using 3-day food records, training volume and leptin responses to a 90-min exercise (measurement before, at the end and after 2 and 24 h of recovery) were assessed at the beginning and at the end of an 8-month training season for heavyweight rowers. RESULTS: During the training, we observed increases in energy intake and in training volume (12.1+/-1.8 and 14+/-1.4 MJ/day, and 3.8+/-1.1 and 6.5+/-1.8 sessions/week, respectively at the beginning and at the end of the season). Carbohydrate (CHO) and protein intakes were increased (P<0.001 and P<0.05, respectively), whereas those of lipid were unchanged (P=0.08). Leptin levels at rest were unchanged, while delayed decreases occurred (at 2 h postexercise) in response to the 90-min exercise (P<0.01). At the end of the season, postexercise and 24 h postexercise leptin levels were positively correlated to CHO intake (r=0.62 and r=0.69, respectively; P<0.05). CONCLUSION: There is an increase in CHO intake over a training season for rowers. Our results suggested that repeated hypoleptinemia in response to acute exercise triggered the particular choice of CHO in order to insure the energy homeostasis.

Effects of chronic exercise on cytokine production in white adipose tissue and skeletal muscle of rats.

White adipose tissue (WAT) is a major source of production of cytokines involved in chronic diseases such as obesity, type 2 diabetes, and atherosclerosis. Long-term exercise has been proposed as a therapy to reduce chronic inflammation. We investigated here the influence of an intense exercise training (over 7 weeks) on several cytokine concentrations including interleukin 1 receptor antagonist (IL-1ra), IL-1beta, and IL-12 in serum, WAT, and skeletal muscle (SM) from non-obese rats. Two groups of 10 rats were investigated: one group was progressively trained (the two last weeks: 120min per day, 25m/min, 7% grade, 5 days per week) and the other age-matched group was used as a sedentary control. Compared to sedentary rats, weight gain was lower in the trained rats (P<0.01). In WAT, concentrations of IL-1ra, IL-1beta, and IL-12 were lower (P<0.001 for IL-1ra and IL-12, P<0.05 for IL-1beta) while they were higher in SM (P<0.01 for IL-1ra, P<0.001 for IL-1beta, P<0.05 for IL-12), and similar in serum. Significant correlations were noted between (i) body weight and WAT concentrations of IL-1ra, IL-1beta, and IL-12 (0.595, 0.450, and 0.481, respectively), (ii) body weight and IL-1beta concentration in SM (-0.526). We also observed significant negative correlations between WAT and SM concentrations of the three cytokines. We show here for the first time that intense exercise training with weight loss reduced concentrations of IL-1ra, IL-1beta, and IL-12 in WAT, while it increased them in SM. These results suggest that exercise could help reduce inflammation in WAT through mobilization of immune cells producing pro- and anti-inflammatory cytokines in SM.

Effects of an intense training on functional activity of 5-HT(1B) receptors in human peripheral blood lymphocytes.

Serotonin (5-HT) is a neurotransmitter and an immune modulator. At the periphery, the serotonergic system appears to possess a regulatory activity via 5-HT 1B receptors. The present study investigated the effects of a 5-day military course following 3 weeks of combat training on the functional activity of 5-HT 1B/1D receptors in peripheral blood lymphocytes of male soldiers. The results of [35S]GTPgammaS binding assays showed that h5-HT 1B/1D receptors were desensitized after the training program, although serum 5-HT was unchanged. These data suggest the existence of a control on T cells mediated through h5-HT 1B/1D receptors leading cytokine production modulation after a physical training.

Intense training: mucosal immunity and incidence of respiratory infections.

This investigation examined the impact of a multistressor situation on salivary immunoglobulin A (sIgA) levels, and incidence of upper respiratory tract infection (URTI) during the French commando training (3 weeks of training followed by a 5-day combat course). For the URTI, the types of symptoms were classified according to the anatomical location of the infection. Saliva samples were collected (8 a.m.) from 21 males [21 (2) years] before entry into the commando training, the morning following the 3 weeks of training, after the 5-day combat course, and after 1 week of recovery. sIgA, protein and cortisol concentrations were measured. Symptoms of URTI were recorded during the study from health logs and medical examinations. After the 3 weeks of training, the sIgA concentration was not changed, although it was reduced after the 5-day course [from 120 (14) mg l(-1) to 71 (9) mg l(-1), P<0.01]. It returned to pre-training levels within a week of recovery. The incidence of URTI increased during the trial (chi(2)=53.48; P<0.01), but was not related to sIgA. Among the 30 episodes of URTI reported, there were 12 rhino-pharyngitis, 6 bronchitis, 5 tonsillitis, 4 sinusitis and 3 otitis. Cortisol levels were raised after the 3-week training (P<0.01), dropping below baseline after the combat course (P<0.01). Stressful situations have an adverse effect on mucosal immunity and incidence of URTI. However, the relationship between sIgA and illness remained unclear. The large proportion of rhino-pharyngitis indicated that the nasopharyngeal cavity is at a higher risk of infection.

Influence of energy deficiency on the insulin-like growth factor I axis in a military training program.

The aim of this study was to determine wether continuous heavy physical activities as well as lack of food and sleep during military training (three weeks of conditioning followed by a five-day combat course) alter serum concentrations of IGF-I and/or its binding proteins, evaluating the relationship to metabolic changes. Before and after training, we measured serum levels of both total and free IGF-I, IGFBP-1 and IGFBP-3 as well as plasma levels of branched-chain amino acids (valine, leucine and isoleucine) and glucose from 26 cadets (21 +/- 2 yr). Total and free IGF-I levels were decreased after training from 228 +/- 12 to 160 +/- 7 ng/ml and from 0.80 +/- 0.08 to 0.52 +/- 0.06 ng/ml, p < 0.001 respectively) as well as IGFBP-3 (p < 0.001), while IGFBP-1 levels were increased (p < 0.001). BCAA levels were decreased from 245.4 +/- 7.5 to 215.9 +/- 5.1 micromol/l, p < 0.001, while those of glucose remained unchanged. There were correlations between changes in total IGF-I and IGFBP-3 (p < 0.05) and between free IGF-I and IGFBP-1 (p < 0.01). Several correlations appeared between changes in all the components of the IGF-I axis and branched-chain amino acids. We concluded that responses of the IGF-I system during an intense training could represent an adaptative response to the encountered energy deficiency, resulting a diversion of substrate from growth to acute metabolic needs.

The effects of long-term adrenalectomy on 5-HT1B receptors mRNA expression in cerebellum, striatum, frontal cortex and hippocampus of rats.

The brain serotonin (5-HT) system and circulating corticosteroids are in close interaction and both implicated in the pathogenesis of affective disorders. We evaluated the effects of adrenalectomy (ADX) on 5-HT(1B) receptors mRNA expression in cerebellum, frontal cortex, striatum and hippocampus in rats, using the RNase protection assay technique. Eight weeks after bilateral adrenalectomy, 5-HT(1B) receptor mRNA levels were decreased in the cerebellum and in the frontal cortex. The expression of 5-HT(1B) receptors mRNA was unchanged in the hippocampus and in the striatum. This data indicates regional differences in the effects of long term adrenalectomy on the expression of 5-HT(1B) receptors.

Effects of moderate and intensive training on the hypothalamo-pituitary-adrenal axis in rats.

The influence of the two distinct training programmes, moderate (M) and intensive (I), on hypothalamo-pituitary-adrenal (HPA) axis was investigated, in rats. Changes in plasma concentrations of adrenocorticotropin hormone (ACTH) and corticosterone were followed in response to (i) a 60-min acute running session performed on 2nd, 4th and 6th of the seven training weeks (ii) an acute restraint stress of 40 min applied after the final training programme. After 2nd, 4th and 6th week of the two training programmes, a 60-min running resulted in an enhanced secretion of ACTH and corticosterone, compared with both the baseline values (i.e. before running) and to the sedentary (S) group. However, on 4th and 6th weeks compared with 2nd week, ACTH and corticosterone remained elevated in intensive group when they are significantly reduced in moderate group. We could suggest that a moderate training resulted in an adapted hormonal response whereas a deadapted process occurred for the intensive programme. The day after the last training session, basal ACTH, corticosterone and corticosteroid-binding globulin (CBG) capacity were not affected by training. Hypothalamic corticotropin-releasing factor tissue-content (CRF) was increased significantly in the two trained groups. When compared with the sedentary group, the body weight of the rats in the two trained groups was significantly decreased with a total adrenal mass increasing but only in intensive group. The surimposed restraint stress resulted in significant increases in plasma ACTH and corticosterone both in trained and in sedentary animals. This result suggests that the adapted HPA axis response induced by both a moderate and intensive training do not prevent against the effects of a novel stress such as restraint stress.

Evidence that the branched-chain amino acid L-valine prevents exercise-induced release of 5-HT in rat hippocampus.

The branched-chain amino acid L-valine competes with tryptophan for transport into the brain and has previously been shown to decrease brain 5-HT synthesis. The purpose of this study was to assess, using a combined venous catheterization and in vivo microdialysis method, the effect of pre-exercise L-valine administration on 5-hydroxytryptamine (5-HT) metabolism in the ventral hippocampus of rats submitted to an acute intensive treadmill running (120 min at 25 m x min(-1) followed by 150 min of recovery). The presented results include measurement of extracellular tryptophan (TRP), the 5-HT precursor, and extracellular 5-hydroxyindoleacetic acid (5-HIAA), the 5-HT metabolite. The data clearly demonstrate that exercise induces 5-HT release in the rat hippocampus: in control group, hippocampal 5-HT levels increase from 123.7 +/- 6.4% at the end of exercise to 133.9 +/- 6.4% after 60 min of recovery. Moreover, two hours of intensive running induced significant increases both in extracellular TRP levels (from 120 min of exercise to 30 min of recovery) and 5-HIAA levels (from 90 min of exercise to 90 min of recovery). Pre-exercise administration of L-valine prevents significantly the exercise-induced 5-HT release: 5-HT levels are maintained to baseline during exercise and recovery. With regard to the competitive effect of L-valine with TRP, we could observe a treatment-induced decrease in brain TRP levels (from 120 min of exercise to the end of recovery). Besides, L-valine does not prevent exercise-induced increase in 5-HIAA levels. The present study evidences that an acute intensive exercise stimulates 5-HT metabolism in the rat hippocampus, and that a pre-exercise administration of L-valine prevents, via a limiting effect on 5-HT synthesis, exercise-induced 5-HT release. This study provides some anwers to previous human and animal investigations, showing physiological and psychological benefits of branched-chain amino acids supplementation on performance.

Endurance training effects on 5-HT(1B) receptors mRNA expression in cerebellum, striatum, frontal cortex and hippocampus of rats.

The 5-HT(1B) receptors are the predominant auto- and heteroreceptors located on serotonergic and non-serotonergic terminals where they regulate the neuronal release of neurotransmitters. The present study investigated the effects of a 7 week period of physical training on the expression of cerebral 5-HT(1B) receptors by measuring corresponding mRNA levels in rat. Using RNase protection assay technique, we have observed no change in 5-HT(1B) receptor mRNA levels in the striatum and in the hippocampus after moderate as well as after intensive training. In contrast, a significant decrease in 5-HT(1B) receptor mRNA levels was observed in cerebellum of intensively trained rats. Moreover, in frontal cortex, a significant decrease in 5-HT(1B) receptors mRNA level occurred in both groups of trained rats. These data suggest the existence of regional differences in the effect of physical exercise on the expression of 5-HT(1B) receptors.