The effect of restraint stress on paradoxical sleep is influenced by the circadian cycle

It is well known that the physiological impact imposed by events or behaviors displayed during the waking period determines the way organisms sleep. Among the situations known to affect sleep both in its duration and quality, stress has been widely studied and it is now admitted that its effects on sleep architecture depend on several factors specific to the stressor or the individual itself. Although numerous reports have highlighted the prominent role of the circadian cycle in the physiological, endocrine and behavioral consequences of restraint stress, a possible circadian influence in the effects of stress on the sleep-wake cycle has never been studied. Thus the present study was designed to compare the effects on sleep of a 1 h-lasting restraint stress applied at light onset to those observed after the same stressor was applied at light offset. We report that in both conditions stress induced a marked paradoxical sleep increase, whereas wakefulness displayed a moderate decrease and slow wave sleep a moderate augmentation. Although the effects of stress at lights on were of similar magnitude than those of stress at lights off, important differences in the sleep rebound latencies were observed: whatever the time of day the stress was applied, its effects on sleep always occurred during the dark period. This result thus shows that restraint stress could be efficiently used to study the interaction between the circadian and homeostatic components of sleep regulation.     

Comparison of the sleep pattern throughout a protocol of chronic sleep restriction induced by two methods of paradoxical sleep deprivation

The purpose of the present study was to evaluate the sleep homeostasis of rats submitted to a protocol of chronic sleep restriction by two methods and to evaluate the sleep characteristics during the recovery period. The sleep restriction protocol was accomplished by sleep depriving rats for 18 h everyday for 21 days, using the single platform method (SPM) or the modified multiple platform method (MMPM) of paradoxical sleep (PS) deprivation. Rats were allowed to sleep for 6 h (from 10:00 to 16:00; starting 3 h after lights on) in their individual home-cages, during which their sleep was recorded. At the end of the sleep restriction protocol, rats were recorded in their home-cages for 4 days, where they could sleep freely. Both methods used to induce chronic sleep restriction were effective, in sofar as they resulted in augmented sleep time during the 6h-sleep period, with very few bouts of wakening. Although comparison between the methods did not reveal differences, sleep restriction under MMPM produced a more consistent daily rebound, mainly of paradoxical sleep, with longer episodes. These results showed distinct sleep recovery patterns, suggesting a possible role of the waking experiences (i.e. immobilization stress, social interaction) acting on sleep consolidation.     

Effects of sleep deprivation on cardiac autonomic and pituitary-adrenocortical stress reactivity in rats

A demanding life style, often associated with restricted time for sleep, is a growing problem in our society and may become a major health issue in the near future. Since the physiological stress system plays a critical role in coping with a challenge, it is important to know whether this system is affected by sleep loss. Although some information is available concerning the effect of sleep loss on the basal activity of the two main limbs of the stress system, the sympathetic-adrenomedullary (SAM) and the hypothalamic-pituitary-adrenocortical (HPA) axes, little is known about the effect of sleep loss on the subsequent response to a stressor. This study investigated the effects of sleep deprivation on cardiac autonomic and HPA axis (re)activity, under baseline conditions and in response to an acute emotional stressor (15-min of restraint). Rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Electrocardiographic recordings were performed via radiotelemetry and autonomic balance was quantified via time-domain indexes of heart rate variability. HPA axis activity was examined by collecting blood samples which were analyzed for plasma ACTH and corticosterone concentrations. The results show that sleep deprivation produced a tonic increase of heart rate and HPA axis activity. When the animals in a state of sleep debt were exposed to an acute restraint stress, a blunted parasympathetic antagonism was observed following sympathetic activation, together with an increased susceptibility to cardiac arrhythmias. The HPA axis response to restraint stress was also altered, but while pituitary ACTH response was attenuated, adrenal corticosterone release was unchanged, indicating an increased adrenocortical sensitivity to ACTH. The data show that sleep deprivation not only affects the baseline activity of the stress system, but it also alters its response to a subsequent stressor.     

The effects of REM sleep-inhibiting drugs in neonatal rats: evidence for a distinction between neonatal active sleep and REM sleep

Neonatal active sleep (AS) has been considered to be homologous and continuous with rapid-eye-movement (REM) sleep in adult animals. We have recently proposed an alternative view that AS is an undifferentiated sleep state distinct from REM sleep. To test these opposing views on the relationship of AS and REM sleep, neonatal rats (P11, P14 and P20) were systemically injected with compounds that inhibit REM sleep in adults. Zimelidine (ZMI) and desipramine (DMI) are monoamine uptake inhibitors which increase synaptic concentrations of serotonin and norepinephrine, respectively. Serotonin and norepinephrine inhibit brainstem cholinergic neurons important in REM sleep generation. Atropine (ATR) is a muscarinic receptor antagonist that blocks the post-synaptic effects of cholinergic projections. Only DMI (5 mg/kg) suppressed AS at P11. ZMI (6 mg/kg) and ATR (6 mg/kg) did not suppress AS until P14. These data suggest that serotonergic and cholinergic regulation of AS are absent before P14. The fact that AS in P11 rats is not affected by cholinergic antagonists supports the hypothesis that AS and REM sleep represent different sleep states.     

Variations in nuchal muscle tonus following paradoxical sleep deprivation in the rabbit

Although tonic inhibition of nuchal or facial musculature is considered an intrinsic component of paradoxical sleep (PS) in mammals, this inhibition is either absent or greatly attenuated in the rabbit. To further explore the characteristics of this phenomenon in this species, variations in quantified nuchal muscle activity were examined before, during and following 24 h of PS deprivation. It was postulated that if the substrate for PS-associated tonic electromyogram (EMG) inhibition is present, this procedure--which is known to affect both tonic and phasic components of PS--might enhance such inhibition. For these investigations chronically implanted rabbits (electroencephalographic, eye movement and nuchal muscle placements) were recorded continuously for 5 consecutive days (two day baseline, one day deprivation, two day recovery). Muscle activity was quantified by resetting integration techniques and comparisons made of activity levels before, during and after PS episodes across conditions. The deprivation procedure significantly reduced the amount of PS relative to baseline values, and a significant PS increase (rebound) occurred during postdeprivation recordings. Across-condition EMG-related effects included the corroboration of previous reports of an absence of nuchal atonia during PS, a significant diurnal variation in EMG activity--with greater activity occurring during the dark portion of the light-dark cycle, and enhanced activity immediately following PS episodes relative to either pre-PS or PS levels. Deprivation-related changes in quantified EMG activity included a pre-PS decrease during both the last 12 h of deprivation and the initial 12 h of recovery sleep, and an enhancement of EMG activity during PS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of social stimuli on sleep in mice: non-rapid-eye-movement (NREM) sleep is promoted by aggressive interaction but not by sexual interaction

Sleep is generally considered to be a process of recovery from prior wakefulness. In addition to being affected by the duration of the waking period, sleep architecture and sleep EEG also depend on the quality of wakefulness. In the present experiment, we examined how sleep is affected by different social stimuli (social conflict and sexual interaction). Male C57BL/6J mice were placed in the cage of an aggressive dominant male or an estrous female for 1 h in the middle of the light phase. The conflict with an aggressive male had a pronounced NREM sleep-promoting effect. EEG slow wave activity, a measure of NREM sleep intensity, was increased for about 6 h and NREM sleep time was significantly increased for 12 h. REM sleep was strongly suppressed during the remainder of the light phase after the conflict, followed by a rebound later in the recovery phase. The sexual interaction, in contrast, had only mild effects. Both NREM sleep and REM sleep were somewhat suppressed shortly after the interaction. In a separate group of mice, blood samples were taken to measure prolactin and corticosterone. The results suggest that the temporary suppression of REM sleep following the social stimuli may be partly due to elevated corticosterone. The different effects of the social stimuli on NREM sleep are not easily explained by differences in the hormone responses. In conclusion, although both social conflict and sexual interaction induce a strong physiological activation, only social conflict has a strong stimulatory effect on NREM sleep mechanisms.     

Effects of prolactin on sleep in cyclic rats

We previously demonstrated that pregnancy-associated sleep enhancement is correlated with the daily surges of prolactin (PRL). However, in spite of a surge of PRL in the proestrous night, a reduction of nocturnal sleep occurs in phase with proestrus. Therefore, to clarify the physiological role of PRL in sleep regulation during the estrous cycle, time-course changes in sleep were analyzed in bromocriptine (CB-154)-treated and/or PRL-supplemented female rats. Sleep patterns characteristic of proestrus-to-estrus were not affected by the CB-154 treatment. In contrast, nocturnal rapid eye movement sleep (REMS) was significantly increased after the PRL supplementation. The CB-154 treatment diminished the REMS-enhancing effect of PRL. Thus, the results suggest that the endogenous PRL is not crucial for the regulation of sleep during the estrous cycle, while exogenous PRL can enhance REMS.     

Effects of different sleep deprivation protocols on sleep perception in healthy volunteers

Objectives

To investigate whether different protocols of sleep deprivation modify sleep perception.

Methods

The effects of total sleep deprivation (TD) and selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception were analyzed in normal volunteers. Thirty-one healthy males with normal sleep were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii) four nights of RD; or (iii) two nights of TD. Morning perception of total sleep time was evaluated for each condition. Sleep perception was estimated using total sleep time (in hours) as perceived by the volunteer divided by the total sleep time (in hours) measured by polysomnography (PSG). The final value of this calculation was defined as the perception index (PI).

Results

There were no significant differences among the three groups of volunteers in the total sleep time measured by PSG or in the perception of total sleep time at baseline condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared with controls during the sleep deprivation period (P < 0.05). Both RD and TD groups showed PI similar to controls during the recovery period.

Conclusion

Selective REM sleep deprivation reduced the ability of healthy young volunteers to perceive their total sleep time when compared with time measured by PSG. The data reinforce the influence of sleep deprivation on sleep perception.     

Release of heat-loss responses in paradoxical sleep by thermal loads and by pontine tegmental lesions in cats

Thermoregulatory heat-loss responses at high ambient temperatures were studied in intact cats and those with bilateral electrolytic lesions in the pontine tegmentum during wakefulness (W), slow-wave sleep (SWS), paradoxical sleep (PS) and PS without atonia induced by the lesions. Panting (respiratory rate 90/min) was present W, SWS, and in some cases, during PS. The percentage of the PS episodes with panting was directly related ambient temperature. In intact cats at 30 °C, panting occurred in 8% of the PS episodes; at 35 °C, in 52%, and at 40 °C, in 77%. The percentage of PS episodes with panting higher in the pontine-lesioned cats (90% at 35 °C), probably another indication of the altered thermoregulation of such animals. Thermoregulatory responses to heat load, and thermoregulation in general, have previously been shown to be suppressed in PS. Because hypothalamic thermosensitive neurons lack thermal responses during PS, the partial activation of heat-loss responses observed here may depend upon the function of extrahypothalamic brainstem areas.     

Glucose attenuation of atropine-induced deficits in paradoxical sleep and memory

When administered systemically, glucose attenuates deficits in memory produced by several classes of drugs, including cholinergic antagonists and opiate agonists. Glucose also enhances memory in aged rats, mice, and humans. In addition, glucose ameliorates age-related reductions in paradoxical sleep. Because deficits in paradoxical sleep are most marked in those individual aged rats that also have deficits in memory, treatments which improve one of these functions may similarly improve the other. The present experiments show that glucose attenuates deficits in paradoxical sleep and memory after atropine administration, with similar dose-response curves for both actions. In the first experiment, rats received saline, atropine (1 mg/kg), glucose (100 mg/kg) or combinations of atropine + glucose (10, 100, 250, and 500 mg/kg) 30 min before assessment on a spontaneous alternation task. In the second experiment, 3-h EEGs were assessed for spontaneous daytime sleep in rats administered saline, atropine (1 mg/kg), glucose (100 mg/kg) or combinations of atropine + glucose (10, 100 and 250 mg/kg). In both experiments, glucose significantly attenuated deficits at an optimal dose of 100 mg/kg. A third experiment assessed blood glucose levels after injections of atropine + glucose (100 mg/kg) and determined that blood glucose levels were similar to those produced by other treatments which enhance memory. These results are consistent with the view that paradoxical sleep and at least one test of memory are similarly influenced by atropine and glucose.     

Enhancement of slow wave sleep parallel to the satiating effect of acidic fibroblast growth factor in rats

Male Wistar rats bearing both chronic cortical electrodes and ICV guide cannula were used. Acidic fibroblast growth factor (aFGF) or vehicle was injected in the lateral ventricle (20, 40, and 80 ng) while EEG and feeding patterns (via microbalance and a computerized monitor) were recorded. Forty and 80, but not 20, ng of aFGF brought about a significant reduction of feeding during 3 h and a dramatic increase of slow wave sleep during 6 h postinjection. Paradoxical sleep remained unchanged. Rectal temperature did not change. These concomitant effects of a single injection of aFGF on feeding and particularly on sleep are similar to the effect of a large meal on the same behavioral parameters.     

Effects of decerebration on blood pressure during paradoxical sleep in cats

We investigated the effects of decerebration on long-term variations in arterial blood pressure during paradoxical sleep (PS) in cats. In normal cats, the blood pressure decreased during the transition from slow wave sleep to PS and maintained its lower level throughout PS for several days after surgery. After this early postoperative stage, however, the arterial hypotension was replaced by tonic and phasic rises in blood pressure during PS. Such long-term changes in blood pressure were completely abolished when the brain stem was transected at the ponto-mesencepholic junction, and the cats consistently exhibited a sustained fall in blood pressure throughout the survival periods of 1 month or more.     

大鼠睡眠剥夺方法的研究进展

目前睡眠的功能并不十分清楚．睡眠研究方法的不足很大程度上制约了睡眠研究及其理论的发展。睡眠剥夺是目前一种很有发展潜力的研究睡眠的手段．它对人们研究睡眠各期的功能有很强的启发性。在睡眠剥夺研究中．要想得到可靠的实验结果．需要有效专一地消除睡眠，因而，消除睡眠的睡眠剥夺方法在研究中有着很重要的意义。本文将几种常用的大鼠睡眠剥夺方法予以综述．     

Effect of paradoxical sleep deprivation on dna synthesis in fetal rat brain

We have investigated the effect of PS-D induced in gestating rats by treatment with clomipramine or with the platform technique on the process of DNA synthesis taking place in fetal organs. This parameter was taken as a biochemical index of ongoing cellular proliferation. In brain and, to a minor extent, in liver and kidney the rate of fetal DNA synthesis was markedly increased in both experimental groups. The effect was more prominent in the clomipramine group. PS-D treatment of gestating rats, notably by the platform technique, left long-lasting effects in the offspring with regard to organ weight and DNA concentration as well as to learning capacity. It is concluded that the occurrence of PS in gestating rats may exert a significant influence on fetal development.     

Chronic stress during paradoxical sleep deprivation increases paradoxical sleep rebound: association with prolactin plasma levels and brain serotonin content

Previous studies suggest that stress associated to sleep deprivation methods can affect the expression of sleep rebound. In order to examine this association and possible mechanisms, rats were exposed to footshock stress during or immediately after a 96-h period of paradoxical sleep deprivation (PSD) and their sleep and heart rate were recorded. Control rats (maintained in individual home cages) and paradoxical sleep-deprived (PS-deprived) rats were distributed in three conditions (1) no footshock - NF; (2) single footshock - SFS: one single footshock session at the end of the PSD period (6-8 shocks per minute; 100ms; 2mA; for 40min); and (3) multiple footshock - MFS: footshock sessions with the same characteristics as described above, twice a day throughout PSD (at 7:00h and 19:00h) and one extra session before the recovery period. After PSD, animals were allowed to sleep freely for 72h. Additional groups were sacrificed at the end of the sleep deprivation period for blood sampling (ACTH, corticosterone, prolactin and catecholamine levels) and brain harvesting (monoamines and metabolites). Neither SFS nor MFS produced significant alterations in the sleep patterns of control rats. All PS-deprived groups exhibited increased heart rate which could be explained by increased dopaminergic activity in the medulla. As expected, PS deprivation induced rebound of paradoxical sleep in the first day of recovery; however, PSD+MFS group showed the highest rebound (327.3% above the baseline). This group also showed intermediate levels of corticosterone and the highest levels of prolactin, which were positively correlated with the length of PS episodes. Moreover, paradoxical sleep deprivation resulted in elevation of the serotonergic turnover in the hypothalamus, which partly explained the hormonal results, and in the hippocampus, which appears to be related to adaptive responses to stress. The data are discussed in the realm of a prospective importance of paradoxical sleep for processing of traumatic events.     

Superfusion of clomipramine within the ventromedial hypothalamus selectively suppresses paradoxical sleep in freely moving rats

Sleep patterns were continuously recorded in rats which received during 2 hours and a half a push-pull superfusion of clomipramine at 10(-6) mol/l or 10(-8) mol/l concentrations, within the ventromedial hypothalamus. The superfusion of 10(-6) mol/l clomipramine resulted in a suppression of paradoxical sleep (PS) and a reduction of slow wave sleep (SWS), whereas lower concentrations of this drug (10(-8) mol/l) suppressed PS but did not affect SWS. In both cases, a secondary rebound of PS was observed. These findings are discussed with regard to the present knowledge of the role of the hypothalamus in sleep.     

REM sleep deprivation-induced deficits in the latency-to-peak induction and maintenance of long-term potentiation within the CA1 region of the hippocampus

Sleep loss adversely affects certain types of cognitive processing, particularly associative memory. Given that long-term potentiation (LTP) represents a putative cellular basis of learning and memory consolidation, the influence of sleep deprivation on LTP was examined. Rats were REM sleep deprived for 24, 48, or 72 h using the inverted flowerpot method in temperature-regulated chambers. Hippocampal slices taken from sleep-deprived rats were compared with home cage and pedestal control animals at 5, 15 and 60 min post-tetanization. The results indicated that at 5 min post-tetanization there were no differences in field potentials in any of the sleep-deprived or control groups, suggesting comparable levels of induction. However, analysis of latency-to-peak slope indicated that members of the 48 and 72 h sleep-deprived groups required approximately twice as long to achieve maximum slope as the 24 h group, home cage or 24, 48, 72 h pedestal controls (means 8.17, 7.50, 2.67, 4.67 and 3.17 min, respectively). At 15 min post-tetanization there were no group differences, however at 60 min post-tetanization the slopes of the field excitatory postsynaptic potentials were significantly diminished for the 24, 48 and 72 h sleep-deprived groups (means 30.44, -1.89, 1.47, respectively) as compared with home cage and pedestal controls (means 59.54, 58.42, respectively). This delay in maximal induction, and the degradation of the maintenance phase of LTP, may represent sleep deprivation-induced impairment of the underlying neurochemical mechanisms normally responsible for memory acquisition.     

Effects of sleep loss on sleep architecture in Wistar rats: gender-specific rebound sleep

This study was designed to examine the influence of gender on sleep rebound architecture after a 4-day paradoxical sleep deprivation period. After a 5-day baseline sleep recording, both male and female rats in different phases of the estrus cycle were submitted to paradoxical sleep deprivation for 96 h. After this period, the sleep rebound recording was evaluated for 5 days (one estrus cycle). The findings revealed that after paradoxical sleep deprivation, sleep efficiency and paradoxical sleep returned to baseline values on the second day of the light period, for all except the proestrus group. During the dark rebound period, only the female groups presented increased sleep efficiency on the first day. Paradoxical sleep returned to baseline values on the third day, except for males and the cycling females submitted to paradoxical sleep deprivation in the diestrus phase, whose baseline values returned to normal on the second day of rebound period. Thus, the females and males displayed distinct patterns as a result of sleep disruption.     

Age-related changes in the sleep pattern of male adult rats

In order to study whether or not the age-related changes in the sleep pattern observed in humans also occur in rats, young adult (4 months) and old (22 months) male Wistar rats were implanted with EEG and EMG electrodes for 24 h on-line registration by means of an automatic sleep-classifier. During the 12 h light period, the old rats as compared to the young adult ones showed a significant increase of the time spent awake and a decrease of active sleep time. Furthermore, the light-dark ratio was decreased in the old rats for wakefulness and active sleep. Off-line analysis of the EEG during quiet sleep and active sleep revealed no differences between the two age groups. These results suggest the existence of a number of considerable age-related changes in the sleep pattern of adult rats, which are comparable to those observed in humans.     

Effects of sleep duration and weekend catch-up sleep on falling injury in adolescents: a population-based study

ObjectiveThis population-based study aimed to determine the effects of sleep deprivation and compensatory weekend catch-up sleep on the risk of falls in adolescents.MethodsData from the 2013 Korean Youth Risk Behavior Web-based Survey on 57,225 adolescents were investigated. Demographic, socioeconomic, sleep-related, health-related behavioral, and psychological variables were compared between fallers (n = 7346) and non-fallers (n = 49,879). Multivariate logistic regression analysis using a hierarchical model was carried out to identify sleep-related factors (eg, sleep duration, longer weekend catch-up sleep) independently contributing to the risk of falls.ResultsCompared to non-fallers, fallers were associated with a shorter sleep duration (p = 0.001) and later bedtimes on weekdays and weekends (p < 0.001). An average sleep duration of ≤ 5 h (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.12–1.34) and of 6 h (OR 1.12, CI 1.03–1.21) were associated with an increased risk of falls. By contrast, an average sleep duration of ≥ 9 h (OR 0.90, CI: 0.82–0.99) and longer weekend catch-up sleep (OR 0.94, CI: 0.89–0.99) were associated with a decreased risk of falls.ConclusionOur results corroborate previous suggestions that short sleep duration is a major risk factor for falls among adolescents. Moreover, our study provided a novel finding that longer sleep duration and longer weekend catch-up sleep may have a protective effect against falls. Our findings have important public health implications that modifying school schedules to increase sleep duration could reduce unintentional falls and injuries in school-aged adolescents.