Subchronic 17alpha-ethinyl estradiol differentially affects subtypes of sleep and wakefulness in ovariectomized rats

In ovariectomized (OVX) Sprague-Dawley rats, estradiol benzoate (EB) has been reported to decrease rapid eye movement (REM) and non-REM (NREM) sleep during the dark phase for up to 3 days. It is unknown, however, if estrogenic effects on sleep extend beyond 3 days or if other estrogens could induce the same changes. Furthermore, it is unclear whether the increased wakefulness in the dark phase was due to changes in active or quiet wakefulness. Therefore, we examined the effects of daily injections of 17alpha-ethinyl estradiol (EE) for 6 days on sleep and wakefulness in the OVX rat. After 3 days of baseline recording using a telemetric system, rats were administered sesame oil (sc) for 3 days followed by injection with EE (20 mug/rat/day, sc) for 6 days. After treatment, sleep was recorded during hormone withdrawal for an additional 5 days. A few sporadic but statistically significant increases in light phase sleep occurred during the last 3 days of EE treatment. Starting on day 2 of the study, EE caused statistically significant decreases in dark phase REM sleep that were maintained throughout the treatment period and persisted until the 3rd day of hormone withdrawal. During the dark phase, statistically significant decreases in NREM sleep and increases in active wakefulness started on the second day of treatment and abated by the end of treatment. This study demonstrated that EE had similar effects on sleep-wakefulness to EB and demonstrates the utility of telemetric polysomnographic recording of the female OVX rat as a model for understanding the estrogen-induced changes on sleep-wakefulness.     

侧脑室注射促甲状腺激素释放激素对大鼠睡眠—觉醒的影响

采用多导睡眠描记术研究了例脑室注射促甲状腺激素释放激素(TRH)对正常大鼠和去甲状腺大鼠睡眠-觉醒的影响。在正常大鼠,TRH引起觉醒增加,浅慢波睡眠(SWS_1)、深慢波睡眠(SWS_2)和总睡眠时间(TST)均减少,异相睡眠(PS)消失,SWS_1、SWS_2和PS的潜伏期均显著延长,给药后立即产生效应并在1h内达高峰。去甲状腺对大鼠的睡眠-觉醒无明显影响,注射TRH后引起的效应与正常大鼠相似。结果提示TRH有促进大鼠觉醒的作用,对各睡眠时相均有抑制作用,其作用部位可能在下丘脑以外的中枢结构。     

Effects of bromocriptine and alpha-flupenthixol on sleep in REM sleep deprived rats.

Administration of bromocriptine mesylate (5 mg/kg, i.p.), a dopamine receptor stimulant, to rats which were deprived of REM sleep for 24 hours resulted in a significant increase in wakefulness as well as significant reduction of REM sleep during the first 5 hours of EEG recording. These effects were completely abolished by pretreatment with α-flupenthixol (0.2 mg/kg, i.p.), a dopamine receptor blocker. The loss of REM sleep has not been regained during the next 25 hours of EEG recording suggesting that the stimulation of dopamine receptors reduced REM sleep without causing subsequent REM rebound. These data raise questions on the negative dopamine control of REM sleep and on the potential use of dopamine stimulants in clinical situations characterized by excessive REM or by REM sleep dysfunction (narcolepsy).     

Cardiopulmonary regulation after rapid-eye-movement sleep deprivation.

Arterial blood pressure, chest movement, electroencephalogram, and electromyogram were monitored in six normotensive Sprague-Dawley rats for 4 h/day 3 days before and 4 days after 114 h of rapid-eye-movement (REM) sleep deprivation. During recovery sleep immediately after REM sleep deprivation (RD), there was a significant increase in the amount of time spent in REM sleep. During this rebound in REM sleep, there was a significant rise (26%) in heart rate in wakefulness, non-REM sleep, and REM sleep during the first 4 h after RD. Systolic blood pressure was also significantly elevated (14%) but only during wakefulness before recovery sleep. Rats with the greatest waking systolic blood pressure after RD had the lowest REM sleep rebound in the 4 h immediately after RD (r = -0.885, P less than 0.05). The rise in heart rate, systolic blood pressure, and REM sleep time evident on day 1 immediately after RD was absent on recovery days 2-4. The respiratory rate tended to be higher throughout the recovery period in every state of consciousness; however, these values never reached the level of significance. In the initial recovery sleep period, regulation of heart rate was more disrupted by REM sleep deprivation than either arterial blood pressure or respiratory rate.     

Rapid-eye movement sleep and muscarinic receptor binding in rats are augmented during withdrawal from chronic scopolamine treatment

The purpose of this study was to determine whether a seven day, once-daily morning administration of scopolamine produces upregulation of muscarinic receptors and augments REMS during withdrawal. After obtaining two, six-hour baseline sleep recordings, beginning at 0900, independent groups of rats were administered either scopolamine or saline every morning for seven days. Six hour sleep recordings were obtained following the first and seventh day of injection and during the two subsequent withdrawal days. After obtaining the last sleep recording the rats were sacrificed and the following brain areas removed: cerebral cortex, hippocampii, caudate nuclei, brainstem, and cerebellum. 3H-QNB was used as the ligand to assess for changes in muscarinic receptor binding. Compared to baseline, scopolamine produced a significant decrease in REMS during the period of drug administration. During the withdrawal days, however, REMS increased during the morning period. Compared to the saline group, the scopolamine treated animals had increased muscarinic receptor binding in the caudate and hippocampus; no significant change in receptor density was observed in the cortex, brainstem or cerebellum.     

Sleep pattern in the rook, Corvus frugilegus

In the rook, Corvus frugilegus, electrographic and behavioural correlates of sleep and wakefulness have been determined under natural lighting conditions. Slow wave sleep (SWS) was characterized by high amplitude slow EEG activity, low neck EMG, and behavioural inactivity. Paradoxical sleep (PS) was characterized by low amplitude fast EEG activity and inconsistent decrease in EMG. PS episodes always commenced with head downward. Several eye movements occurred activity were present. The rook spent in sleep 31.8% of the 24-h period. PS however, eye movements, high tonic neck EMG activity, and behavioural activity were present. The rook spent in sleep 31.8% of the 24-h period. PS constituted 1.8% of total sleep, while the rest of total sleep was occupied by SWS. On the average, episodes of SWS and PS lasted 10.8 min and 24 s respectively. The daily percentage of SWS was highly correlated with the mean episode duration. PS amount was better correlated with the number of episodes than with their mean duration. Our data suggest that over-short period of recovery from surgery and adaptation with implanted electrodes could lead to underestimation of sleep duration in rook.     

Spontaneous sleep and homeostatic sleep regulation in ghrelin knockout mice

Ghrelin is well known for its feeding and growth hormone-releasing actions. It may also be involved in sleep regulation; intracerebroventricular administration and hypothalamic microinjections of ghrelin stimulate wakefulness in rats. Hypothalamic ghrelin, together with neuropeptide Y and orexin form a food intake-regulatory circuit. We hypothesized that this circuit also promotes arousal. To further investigate the role of ghrelin in the regulation of sleep-wakefulness, we characterized spontaneous and homeostatic sleep regulation in ghrelin knockout (KO) and wild-type (WT) mice. Both groups of mice exhibited similar diurnal rhythms with more sleep and less wakefulness during the light period. In ghrelin KO mice, spontaneous wakefulness and rapid-eye-movement sleep (REMS) were slightly elevated, and non-rapid-eye-movement sleep (NREMS) was reduced. KO mice had more fragmented NREMS than WT mice, as indicated by the shorter and greater number of NREMS episodes. Six hours of sleep deprivation induced rebound increases in NREMS and REMS and biphasic changes in electroencephalographic slow-wave activity (EEG SWA) in both genotypes. Ghrelin KO mice recovered from NREMS and REMS loss faster, and the delayed reduction in EEG SWA, occurring after sleep loss-enhanced increases in EEG SWA, was shorter-lasting compared with WT mice. These findings suggest that the basic sleep-wake regulatory mechanisms in ghrelin KO mice are not impaired and they are able to mount adequate rebound sleep in response to a homeostatic challenge. It is possible that redundancy in the arousal systems of the brain or activation of compensatory mechanisms during development allow for normal sleep-wake regulation in ghrelin KO mice.     

Neurophysiological analysis of the effects of partial paradoxical sleep deprivation

A neurophysiological study was made of the effects of partial and complete paradoxial sleep deprivation by substituting episodes of active wakefulness for spells of paradoxical sleep (PS) of the same duration in the sleep-wake cycle. Neither accumulated need for paradoxical sleep (culminating in increased onset of PS during deprivation), PS rebound during the post-deprivation period, nor dissociation of the stages of paradoxical sleep resulting in their intervening individually at unaccustomed points in the sleep-wake cycle were observed during our experimental procedure. The phenomenon of self-deprivation, increased heart rate, eye movements, and pontogeniculooccipital (PGO) action potentials also failed to occur during the post-deprivation period. It is postulated that PS requirement and the need for periods of wakefulness stem from the same neurochemical alterations.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 20–28, January–February, 1988.     

Effects of clozapine (Leponex) on sleep patterns in the cat.

This study examined the effects of clozapine on sleep-wakefulness profile in cats prepared for chronic recording of sleep. Clozapine in single dose (i.p.) of 5 mg/kg drastically reduced slow-wave sleep (SWS) and paradoxical sleep (PS), while wakefulness and drowsy pattern were increased. These changes lasted approximately 24 h and were followed by sleep recovery. PS had a priority of recovery. Some similarities between clozapine effects on sleep in cat and human were mentioned.     

Ozone-induced paradoxical sleep decrease is related to diminished acetylcholine levels in the medial preoptic area in rats

Ozone (O3) produces significant effects on sleep, characterized specially by a decrease in paradoxical sleep (PS) and increase in slow-wave sleep (SWS), which in turn represent a sleep-wake cycle disruption. On the other hand, neuronal activity recorded in the cholinoceptive hypothalamic medial preoptic area (MPO) has been involved in the regulation of sleep. However, there is no direct evidence on the role that acetylcholine (Ach) release in the MPO plays in the sleep-wake cycle. In order to study this relation, we measured the Ach concentration in dialysates collected from MPO in rats exposed to coal-filtered air (clean air) for 48 h and in rats exposed to clean air for 24 h followed by 24-h of O3 exposure to 0.5 ppm. Polygraphic sleep records were taken simultaneously to neurochemical sampling. O3 was employed to disrupt the sleep-wake cycle and relate these changes with concomitant disruptions in Ach concentration dialyzed from MPO. A clear circadian pattern of Ach concentration was observed in dialysates from MPO and also in PS, SWS and wakefulness of rats exposed to filtered air. However, O3 exposure decreased the PS by 65% (Mann-Whitney's U-test, p相似文献   

Two Anti-anxiety Drugs: A Psychoneuroendocrine Study

Eight males were studied during 27 weeks, including two periods of five weeks during which they received clinical doses of sodium amylobarbitone and benzoctamine. Substitution of placebo for either drug caused raised anxiety and impairment of mental concentration. The drugs reduced restlessness during sleep and reduced paradoxical sleep. By the fifth week of sodium amylobarbitone, although sleep was still less restless in the early night it was more restless than normal in the late night.Blood samples were taken half-hourly during sleep by indwelling venous catheter. Plasma growth hormone concentration was little affected during drug administration but rose temporarily after withdrawal. There was a reduction of plasma corticosteroid concentration during sleep throughout administration of the drugs and a rebound above normal during the first withdrawal week.     

Compensatory sleep response to 12 h wakefulness in young and old rats

There is a pronounced decline in sleep with age. Diminished output from the circadian oscillator, the suprachiasmatic nucleus, might play a role, because there is a decrease in the amplitude of the day-night sleep rhythm in the elderly. However, sleep is also regulated by homeostatic mechanisms that build sleep drive during wakefulness, and a decline in these mechanisms could also decrease sleep. Because this question has never been addressed in old animals, the present study examined the effects of 12 h wakefulness on compensatory sleep response in young (3.5 mo) and old (21.5 mo) Sprague-Dawley and F344 rats. Old rats in both strains had a diminished compensatory increase in slow-wave sleep (SWS) after 12 h of wakefulness (0700-1900, light-on period) compared with the young rats. In contrast, compensatory REM sleep rebound was unaffected by age. To assess whether the reduced SWS rebound in old rats might result from loss of neurons implicated in sleep generation, we counted the number of c-Fos immunoreactive (c-Fos-ir) cells in the ventral lateral preoptic (VLPO) area and found no differences between young and old rats. These findings indicate that old rats, similar to elderly humans, demonstrate less sleep after prolonged wakefulness. The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep.     

Geniohyoid muscle activity in normal men during wakefulness and sleep

Reduction in the activity of upper airway "dilator" muscles during sleep may allow the pharyngeal airway to collapse in some individuals. However, quantitative studies concerning the effect of sleep on specific upper airway muscles that may influence pharyngeal patency are sparse and inconclusive. We studied seven normal men (mean age 27, range 22-37 yr) during a single nocturnal sleep study and recorded sleep staging parameters, ventilation, and geniohyoid muscle electromyogram (EMGgh) during nasal breathing throughout the night. Anatomic landmarks for placement of intramuscular geniohyoid recording electrodes were determined from a cadaver study. These landmarks were used in percutaneous placement of wire electrodes, and raw and moving-time-averaged EMGgh activities were recorded. Sleep stage was determined using standard criteria. Stable periods of wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep were selected for analysis. The EMGgh exhibited phasic inspiratory activity during wakefulness and sleep in all subjects. In six of seven subjects, mean and peak inspiratory EMGgh activities were significant (P less than 0.05) reduced during stages 2 and 3/4 NREM sleep and REM sleep compared with wakefulness. This reduction of EMGgh activity was shown to result from a sleep-related decline in the level of tonic muscle activity. Phasic inspiratory EMGgh activity during all stages of sleep was not significantly different from that during wakefulness. Of interest, tonic, phasic, and peak EMGgh activities were not significantly reduced during REM sleep compared with any other sleep stage in any subject. In addition, the slope of onset of phasic EMGgh activity was not different during stage 2 NREM and REM sleep compared with wakefulness in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dihydroergotoxine methane sulphonate (Redergine) on sleep in cats deprived of paradoxical sleep

Dihydroergotoxine methane sulphonate (DHET 1.0 mg/kg i.p.) was administered to cats deprived of paradoxical sleep (PS) for 72 h and 23 h of recovery sleep were recorded. During the first 12 h of recovery sleep slow-wave sleep (SWS) was significantly increased. There were no significant changes in the amounts of wakefulness (W), PS and several sleep indices. Analysis of the entire 23 h of recording period revealed no significant changes in any of the parameters studied. The results suggest that DHET has SWS enhancing property in the condition where "pressure" for PS was increased.     

Dueling Hypotheses: Circatidal Versus Circalunidian Battle Basics–Second Engagement

The daily rhythm in body temperature is thought to be the result of the direct effects of activity and the effects of an endogenous circadian clock. Forced desynchrony (FD) is a tool used in human circadian rhythm research to disentangle endogenous and activity-related effects on daily rhythms. In the present study, we applied an FD protocol to rats. We subjected 8 rats for 5 days to a 20h forced activity cycle consisting of lOh of forced wakefulness and lOh for rest and sleep. The procedure aimed to introduce a lOh sleep/ lOh wake cycle, which period was different from the endogenous circadian (about 24h) rhythm. Of the variation in the raw body temperature data, 68–77% could be explained by a summation of estimated endogenous circadian cycle and forced activity cycle components of body temperature. Free-running circadian periods of body temperature during FD were similar to free-running periods measured in constant conditions. The applied forced activity cycle reduced clock-related circadian modulation of activity. This reduction of circadian modulation of activity did not affect body temperature. Also, the effects of the forced activity on body temperature were remarkably small.     

Forced Desynchrony of Orcadian Rhythms of Body Temperature and Activity in Rats

The daily rhythm in body temperature is thought to be the result of the direct effects of activity and the effects of an endogenous circadian clock. Forced desynchrony (FD) is a tool used in human circadian rhythm research to disentangle endogenous and activity-related effects on daily rhythms. In the present study, we applied an FD protocol to rats. We subjected 8 rats for 5 days to a 20h forced activity cycle consisting of lOh of forced wakefulness and lOh for rest and sleep. The procedure aimed to introduce a lOh sleep/ lOh wake cycle, which period was different from the endogenous circadian (about 24h) rhythm. Of the variation in the raw body temperature data, 68-77% could be explained by a summation of estimated endogenous circadian cycle and forced activity cycle components of body temperature. Free-running circadian periods of body temperature during FD were similar to free-running periods measured in constant conditions. The applied forced activity cycle reduced clock-related circadian modulation of activity. This reduction of circadian modulation of activity did not affect body temperature. Also, the effects of the forced activity on body temperature were remarkably small.     

The effect of multiple audiogenic seizures upon the sleep organization in rats

The organization of sleep during and after frequentative convulsions, consisting of 2, 3, or 5 comparatively rare seizures (following one another with a 90-minute interval) or of 3, 5 or 9 comparatively frequent seizures (following one another with a 45-minute interval) of generalized tonic-clonic character in Krushinskii-Molodkina strain rats with inherited predisposition to audiogenic convulsions, was studied. In frequentative convulsions with rare seizures, between separate seizures, passive wakefulness (75.2 +/- 4.6% time) prevailed under low (24.8 +/- 4.3%) slow-wave sleep and full absence of fast-wave sleep. In rats under frequentative convulsions with frequent seizures, in interictal period, only passive wakefulness was observed under reduction of slow-wave sleep and fast-wave sleep, i.e. total sleep deprivation. Minimal latensy of first episodes of the slow-wave sleep after frequentative convulsions was 59.9 +/- 10.8, and of fast-wave sleep: 158.2 +/- 13.4 min. First episodes of slow-wave sleep and fast-wave sleep had normal structure, though they were lesser and shorter than in control experiments. In spite of long-lasting (up to 7 hrs) absence of slow-wave sleep during seizure and prolonged (8.5 hrs) reduction of fast-wave sleep with no subsequent compensatory increase, these conditions occurred in the wakefulness-sleep cycle during 12-hour reconstruction after convulsions. The reconstruction period after frequentative convulsions was characterized by increase in general share of wakefulness and reduction of total slow-wave and fast-wave sleep as compared with control data. Paroxysmal status seems to disorganize work of the brain somnogenic structures. The function of systems responsible for slow-wave sleep are affected to a lesser extent, but disorganization of the system responsible for fast-wave sleep is more significant and associated with mechanisms of starting the phase of sleep in the first place.     

Effects of [des-Tyr-D-Phe3]beta-casomorphin (2-5) on sleep pattern in rats.

The effects of the antidepressant-like acting peptide [des-Tyr-D-Phe3]beta-casomorphin(2-5) (Pro-D-Phe-Pro-Gly, BCH-325) on sleep were studied in rats. The rats received subcutaneous injections of BCH-325 in acute experiments (doses: 4, 20, 100, 500 and 2500 nmol/kg) and in a 10-day chronic experiment (50 nmol/kg/day). Acute administration of 20 and 100 nmol/kg enhanced wakefulness, 500 and 2500 nmol/kg enhanced paradoxical sleep, and 4 nmol/kg had no effect. Chronic administration resulted in an increase of paradoxical sleep during the first 5 days of drug treatment. Thus the sleep effects of BCH-325 differ from those of typical antidepressants and other psychotropic drugs.     

Diaphragm long-term facilitation following acute intermittent hypoxia during wakefulness and sleep

Acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Here, we tested four hypotheses in unanesthetized, spontaneously breathing rats using radiotelemetry for EEG and diaphragm electromyography (Dia EMG) activity: 1) AIH induces LTF in Dia EMG activity; 2) diaphragm LTF (Dia LTF) is more robust during sleep vs. wakefulness; 3) AIH (or repetitive AIH) disrupts natural sleep-wake architecture; and 4) preconditioning with daily AIH (dAIH) for 7 days enhances Dia LTF. Sleep-wake states and Dia EMG were monitored before (60 min), during, and after (60 min) AIH (10, 5-min hypoxic episodes, 5-min normoxic intervals; n = 9), time control (continuous normoxia, n = 8), and AIH following dAIH preconditioning for 7 days (n = 7). Dia EMG activities during quiet wakefulness (QW), rapid eye movement (REM), and non-REM (NREM) sleep were analyzed and normalized to pre-AIH values in the same state. During NREM sleep, diaphragm amplitude (25.1 ± 4.6%), frequency (16.4 ± 4.7%), and minute diaphragm activity (amplitude × frequency; 45.2 ± 6.6%) increased above baseline 0-60 min post-AIH (all P < 0.05). This Dia LTF was less robust during QW and insignificant during REM sleep. dAIH preconditioning had no effect on LTF (P > 0.05). We conclude that 1) AIH induces Dia LTF during NREM sleep and wakefulness; 2) Dia LTF is greater in NREM sleep vs. QW and is abolished during REM sleep; 3) AIH and repetitive AIH disrupt natural sleep patterns; and 4) Dia LTF is unaffected by dAIH. The capacity for plasticity in spinal pump muscles during sleep and wakefulness suggests an important role in the neural control of breathing.     

Auditory deprivation modifies biological rhythms in the golden hamster

To assess to what extent auditory sensory deprivation affects biological rhythmicity, sleep/wakefulness cycle and 24 h rhythm in locomotor activity were examined in golden hamsters after bilateral cochlear lesion. An increase in total sleep time as well as a decrease in wakefulness (W) were associated to an augmented number of W episodes, as well as of slow wave sleep (SWS) and paradoxical sleep (PS) episodes in deaf hamsters. The number of episodes of the three behavioural states and the percent duration of W and SWS increased significantly during the light phase of daily photoperiod only. Lower amplitudes of locomotor activity rhythm and a different phase angle as far as light off were found in deaf hamsters kept either under light-dark photoperiod or in constant darkness. Period of locomotor activity remained unchanged after cochlear lesions. The results indicate that auditory deprivation disturbs photic synchronization of rhythms with little effect on the clock timing mechanism itself.