Effect of ambient temperature on the 24-hour sleep-wake cycle in normal and capsaicin-treated rats

The 24-hour sleep-wake cycle of untreated, normal rats and of capsaicin-treated rats was continuously recorded by telemetry. Recordings were made on two baseline days at 22 degrees C, two days at 29 degrees C, and two final days at 22 degrees C. In untreated animals the daily amount of waking was reduced by the elevated ambient temperature and nonREM sleep was enhanced. This effect was mainly due to the frequent interruption of the dark-time waking episodes by sleep. In capsaicin-treated animals, raising the ambient temperature did not significantly enhance sleep. However, in both groups of rats the slow wave sleep (SWS) fraction of nonREM sleep was increased after elevating the temperature to 29 degrees C. REM sleep showed a minor increase which was significant only for the capsaicin-treated group. The results suggest that a moderate increase of ambient temperature has two effects: (1) It causes an enhancement of sleep by a reduction in the duration of waking episodes, an effect that may represent a heat-defense response. The attenuation of this response in capsaicin-treated rats may be a consequence of the impairment of warm-receptors. (2) It favors the occurrence of SWS and REM sleep.     

Brief skin temperature changes towards thermoneutrality trigger REM sleep in rats

When rats were in slow-wave sleep (SWS) at an environmental temperature (23°C) below their thermoneutral zone (27–31°C), brief skin warming by either radiant heating, or forced air convection resulted in REM sleep on 79–80% of the trials. During control nonwarmed SWS bouts, the animals went into REM sleep on only 22–24% of the trials. When the environmental temperature was above thermoneutrality, 34°C, lowering skin temperature by convective cooling resulted in REM sleep entry 68% of the time, compared to 21% for noncooled, control trials. Skin warming and cooling at 29°C decreased the percent occurrence of REM sleep to 22% and 9% respectively, for at this thermoneutral temperature 46% of the control SWS bouts ended in REM sleep. Thus, peripheral temperature changes towards thermoneutrality trigger REM sleep in mildly thermally stressed rats.     

Prazosin modulates rapid eye movement sleep deprivation-induced changes in body temperature in rats

Prolonged rapid eye movement sleep deprivation (REMSD) causes hypothermia and death; however, the effect of deprivation within 24 h and its mechanism(s) of action were unknown. Based on existing reports we argued that REMSD should, at least initially, induce hyperthermia and the death upon prolonged deprivation could be due to persistent hypothermia. We proposed that noradrenaline (NA), which modulates body temperature and is increased upon REMSD, may be involved in REMSD- associated body temperature changes. Adult male Wistar rats were REM sleep deprived for 6–9 days by the classical flower pot method; suitable free moving, large platform and recovery controls were carried out. The rectal temperature (Trec) was recorded every minute for 1 h, or once daily, or before and after i.p. injection of prazosin, an alpha-1 adrenergic antagonist. The Trec was indeed elevated within 24 h of REMSD which decreased steadily, despite continuation of deprivation. Prazosin injection into the deprived rats reduced the Trec within 30 min, and the duration of effect was comparable to its pharmacological half life. The findings have been explained on the basis of REMSD-induced elevated NA level, which has opposite actions on the peripheral and the central nervous systems. We propose that REMSD-associated immediate increase in Trec is due to increased Na-K ATPase as well as metabolic activities and peripheral vasoconstriction. However, upon prolonged deprivation, probably the persistent effect of NA on the central thermoregulatory sites induced sustained hypothermia, which if remained uncontrolled, results in death. Thus, our findings suggest that peripheral prazosin injection in REMSD would not bring the body temperature to normal, rather might become counterproductive.     

Promotion of sleep by heat in young rats

The aim of the experiments was to study the effects of a moderate heat load on sleep in young (26-day-old) rats and to determine whether the sleep-promoting effect of heat results from stimulation of the homeostatic sleep process. The changes in sleep-wake activity, electroencephalogram slow wave activity (SWA) during non-rapid eye movement sleep (NREMS) and cortical temperature (T _crt) were determined during and after long (24-h) and short (2.5-h) heat loads (elevation of ambient temperature from 26° C to 32° C), and after total sleep deprivation (SD) combined with a short-term heat load. The heat exposures elicited increases in T _crt and rectal temperature (2 and 1.7° C respectively). The long-term heat load induced persistent, albeit slight enhancements in NREMS. Rapid eye movement sleep (REMS) increased with a 12-h delay during the 24-h heat load. Heat elicited an immediate large increase in SWA. After this initial increase, SWA declined and tended to fall below the baseline level during the last 12 h of the 24-h heat load. SWA and REMS were significantly suppressed after termination of 24-h heat loading. The increased SWA during the short-term heat load was not followed by subsequent alterations in sleep when the ambient temperature had returned to normal. However, after the combination of SD with the shortterm heat load the durations of NREMS and SWA were significantly enhanced compared with those found after SD at 26° C. The results are interpreted as suggesting that heat increases NREMS in the young rat by the same mechanism as is involved in the enhancement of NREMS after SD: a stimulation of sleep drive.     

Non-REM sleep as a source of learning deficits induced by REM sleep deprivation.

Procedures that deprive animal subjects of rapid eye movement sleep have often been associated with learning impairments. Previously, the conclusion has been drawn that these learning impairments are due to the absence of some positive function of rapid eye movement sleep. The present research indicates more precisely that typical impairments associated with the deprivation procedures may be due to isolated periods of non-REM sleep, rather than due to the simple absence of rapid eye movement sleep. Mice were tested for acquistion of a complex maze task, and subjected to post-trial rapid eye movement sleep deprivation by the pedestal method. Only animals demonstrating (non-REM) sleep behaviors during deprivation gave evidence of learning deficits.     

Slow wave sleep enhancement with gaboxadol reduces daytime sleepiness during sleep restriction

STUDY OBJECTIVES: To evaluate the impact of enhanced slow wave sleep (SWS) on behavioral, psychological, and physiological changes resulting from sleep restriction. DESIGN: A double-blind, parallel group, placebo-controlled design was used to compare gaboxadol (GBX) 15 mg, a SWS-enhancing drug, to placebo during 4 nights of sleep restriction (5 h/night). Behavioral, psychological, and physiological measures of the impact of sleep restriction were assessed in both groups at baseline, during sleep restriction and following recovery sleep. SETTING: Sleep research laboratory. PARTICIPANTS: Forty-one healthy adults; 9 males and 12 females (mean age: 32.0 +/- 9.9 y) in the placebo group and 10 males and 10 females (mean age: 31.9 +/- 10.2 y) in the GBX group. INTERVENTIONS: Both experimental groups underwent 4 nights of sleep restriction. Each group received either GBX 15 mg or placebo on all sleep restriction nights, and both groups received placebo on baseline and recovery nights. MEASUREMENTS AND RESULTS: Polysomnography documented a SWS-enhancing effect of GBX with no group difference in total sleep time during sleep restriction. The placebo group displayed the predicted deficits due to sleep restriction on the multiple sleep latency test (MSLT) and on introspective measures of sleepiness and fatigue. Compared to placebo, the GBX group showed significantly less physiological sleepiness on the MSLT and lower levels of introspective sleepiness and fatigue during sleep restriction. There were no differences between groups on the psychomotor vigilance task (PVT) and a cognitive test battery, but these measures were minimally affected by sleep restriction in this study. The correlation between change from baseline in MSLT on Day 6 and change from baseline in SWS on Night 6 was significant in the GBX group and in both group combined. CONCLUSIONS: The results of this study are consistent with the hypothesis that enhanced SWS, in this study produced by GBX, reduces physiological sleep tendency and introspective sleepiness and fatigue which typically result from sleep restriction.     

Cold exposure and sleep in the rat: REM sleep homeostasis and body size

STUDY OBJECTIVES: Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24 degrees C. DESIGN: EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10 degrees C to -10 degrees C and for 4 days during recovery. SETTING: Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. SUBJECTS: 24 male albino rats. INTERVENTIONS: Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature. MEASUREMENTS AND RESULTS: REMS occurrence decreased proportionally with cold exposure, but a fast compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond a "fast rebound" threshold corresponding to 22% of the daily REMS need. A slow REMS rebound apparently allowed the animals to fully restore the previous REMS loss during the following 3 days of recovery. CONCLUSION: Comparing the present data on rats with data from earlier studies on cats and humans, it appears that small mammals have less tolerance for REMS loss than large ones. In small mammals, this low tolerance may be responsible on a short-term basis for the shorter wake-sleep cycle, and on long-term basis, for the higher percentage of REMS that is quickly recovered following REMS deprivation.     

Prenatal malnutrition and sleep states in adult rats: effects of restraint stress

Independently, prenatal malnutrition and psychological/physical stress have been shown to affect sleep architecture in adult rats. As malnutrition and stress commonly co-exist in malnourished human populations, the objective of the present study was to ascertain the combined effects of these two insults by examining sleep-wake parameters following a brief restraint stress in prenatally protein malnourished rats. The male offspring of rats provided with a protein deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy were implanted with recording electrodes beginning at postnatal day 90. Polygraph recordings were obtained to quantify sleep states during the first 4 h of the dark phase of the cycle on 2 consecutive days. The first followed a 24-h habituation session to the recording chamber (baseline). The second occurred at the same time of day but followed 20 min of restraint stress in a Plexiglas tube. During baseline, prenatally malnourished rats spent more time in rapid eye movement sleep (REMS) in the first 2 h after "lights off" (block 1), and greater amounts of wakefulness (W) with a corresponding reduction in slow wave sleep (SWS) in the second two hours (block 2), as compared with controls. Following stress, the sleep architecture of both groups of rats remained unaltered in block 1 relative to their baseline day. In block 2, both groups exhibited significant reductions in SWS and REMS with significantly greater reductions being expressed in the prenatally malnourished group (most dramatically, REMS was completely eliminated). These findings suggest that sleep disturbances may be more severe in those malnourished human populations subjected to acutely stressful experiences.     

Different types of avoidance behavior in rats produce dissociable post-training changes in sleep

Avoidance learning affects post-training sleep, and post-training sleep deprivation impairs performance. However, not all rats learn to make avoidance responses, and some rats fail to escape; a definitive behavior of learned helplessness, a model of depression. This study investigated the changes in sleep associated with different behaviors adopted following avoidance training. Rats (n = 53) were trained for 100 trials over 2 days (50 trials/day), followed by 23-24 h of post-training polysomnography, then re-tested (25 trials). At re-test, rats were categorized into: 1) Active Avoiders (AA; n = 22), 2), Non-learning (NL; n = 21), or 3) Escape Failures (EF; n = 10). AA rats increased avoidances over days, whereas the NL and EF groups did not. EF rats increased escape failures over days, whereas the NL and AA rats did not. EF rats had increased rapid eye movement (REM) sleep in the first 4 h on training day 1. They also had increased non-REM sleep in the first 4 h and last 4 h on both training days. AA rats had increased REM sleep 13-20 h post-training. The type of behavioral strategy adopted throughout training is associated with a unique pattern of changes in post-training sleep. Training-dependent changes in post-acquisition sleep may reflect distinct processes involved in the consolidation of these different memory traces.     

Changes in sleep theta rhythm are related to episodic memory impairment in early Alzheimer's disease

Impairments have been reported both in sleep structure and episodic memory in Alzheimer's disease [AD]. Our objective was to investigate the relationships between episodic memory deficits and electro-encephalography [EEG] abnormalities occurring during sleep in patients with early AD. Postlearning sleep was recorded in 14 patients with mild to moderate AD, and 14 healthy elderly controls after they performed an episodic memory task derived from the Grober and Buschke's procedure. For each sleep stage, the relative power and mean frequency in each band were analyzed. Relative to agematched controls, AD patients presented faster mean theta frequency in both REM sleep and slow wave sleep [SWS]. In AD patients, a correlative analysis revealed that faster theta frequency during SWS was associated with better delayed episodic recall. We assume that increased theta activity reflects changes in neuronal activity to maintain memory performance, indicating that compensatory mechanisms already described at the waking state could also be engaged during SWS.     

The effect of the timing, quality and quantity of sleep upon the depression (masking) of body temperature on an irregular sleep/wake schedule

SUMMARY  Eight subjects were studied on an irregular sleep/wake schedule which was designed so that prior wake time and the time of day when 4-h sleep periods were taken were both balanced. Rectal temperature and the sleep EEG were measured throughout the 8-d protocol. A purification method was used to estimate the depression of rectal temperature (masking) caused by the first and second halves of each 4-h sleep period. On average this was 0.187 ± 0.015°C during the first 2h and 0.262 ± 0.017°C during the second 2h. Masking increases beyond the first 2 h of sleep, but any effects due to the phase of the rectal temperature when sleep is taken are very weak. However, masking did increase (that is, the temperature was depressed more) when the amount of prior wake time was greater than 4 h. When the effects of sleep content variables were considered also, masking was still greater in the second half of sleep and tended to increase with the amount of slow-wave sleep, but it decreased with increasing amounts of time awake during a sleep period (sleep latency or sleep discontinuity). Some implications of these results for the mechanism of sleep-induced masking are considered.     

Cold exposure impairs dark-pulse capacity to induce REM sleep in the albino rat

In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during exposure to low ambient temperature (Ta). To this aim, the efficiency of a non-rhythmical repetitive DP (3 min each) delivery during the first 6-h light period of a 12 h:12 h light-dark cycle in inducing REMS was studied in the rat, through the analysis of electroencephalogram, electrocardiogram, hypothalamic temperature and motor activity at different Tas. The results showed that DP delivery triggers a transition from NREMS to REMS comparable to that which occurs spontaneously. However, the efficiency of DP delivery in inducing REMS was reduced during cold exposure to an extent comparable with that observed in spontaneous REMS occurrence. Such impairment was associated with low Delta activity and high sympathetic tone when DPs were delivered. Repetitive DP administration increased REMS amount during the delivery period and a subsequent negative REMS rebound was observed. In conclusion, DP delivery did not overcome the integrative thermoregulatory mechanisms that depress REMS in the cold. These results underline the crucial physiological meaning of the mutual exclusion of thermoregulatory activation and REMS occurrence, and support the hypothesis that the suspension of the central control of body temperature is a prerequisite for REMS occurrence.     

Effects of rearing environments upon sleep-waking parameters in rats

Effects of environmentally different rearing conditions upon sleep-waking parameters were studied in Long-Evans hooded rats. Male littermates were assigned to enriched (EC), standard colony (SC) and impoverished conditions (IC) at 50–60 days old and kept under each condition for 30–50 days. Polygraphic recordings revealed that the ratio of arousal time to total recording time (%Ar) decreased, and that percent slow wave sleep (%SS), percent paradoxical sleep (%PS) and mean PS duration increased significantly in EC animals compared to SC and IC groups during the night (18.00–06.00 hr). The ratio of PS to total sleep time (PS/TS) was similar in the three groups. The EC changes disappeared during the day (06.00–18.00 hr) in all items studied except for the mean PS duration. The EC-IC difference was found to be mainly due to EC and not to IC.     

REM sleep deprivation and food competition in male rats

As a test of the hypothesis that REM deprivation lowers the threshold for “motivational” behaviors, 17 male rats that had been REM deprived were tested against 17 non-deprived male rats in three series of food competition tests, i.e., an immediate, a 3 hr, and a 48 hr series of posttreatment tests. The results provide support for the hypothesis that REM deprivation generally activates “motivational” behaviors, in that the REM deprived animals won more frequently as had been predicted. However, the response gradients of the two groups over the course of the postteatment test series did not conform to prediction. These data are discussed together with the results of other studies which suggest that perhaps the list of behaviors which have been subsumed under the category—“motivational behaviors” is too broad to be of real scientific value.     

Slow Wave Sleep Deficiency Insomnia: A Problem in Thermo-Downregulation at Sleep Onset

The following review article attempts to develop the argument that a regulated, rapid drop in rectal, core-body temperature following sleep onset is a necessary prerequisite to the presence of sustained slow wave sleep (NREM Stage 4). Based upon this premise, a theory1 is presented to suggest that the slow wave sleep deficiency so commonly associated with chronic, primary insomnia (Gaillard, 1976, 1978) is the result of a failure in the thermoregulatory system to show a regulated, rapid decrease in body temperature with sleep onset which persists for the first 1–2 hrs into the sleep period.     

Brain and core temperatures and peripheral vasomotion during sleep and wakefulness at various ambient temperatures in the rat

Changes in brain, core and tail skin temperatures (T _br, T _c and T _t) associated with transitions in the arousal states were recorded in rats throughout the 24-h diurnal cycle at 10 °C, 21 °C and 29 °C. Falling asleep was accompanied by decreases in both T _br and T _c and vasodilation at 10 C and 21 °C. At 29 °C, tail vessels were permanently dilated, and further dilation was not found on sleep onset. T _br and T _c, however, continued to decrease during non-rapid-eye-movement sleep (NREMS); these changes are likely to result from reductions in heat production and increased conductive heat loss. The changes in T _br, T _c and T _t on awakening mirrored those on falling asleep. It is suggested that the suppression of sleep in the cold and the enhancement of NREMS in the heat promote thermoregulation. Rapid-eye-movement sleep (REMS) was associated with sharp rises in T _br. The rise in T _br was the largest in the cold and was attenuated at 29 °C. T _c decreased and T _t increased in the cold, whereas T _c tended to increase and T _t to decrease in the heat. The paradoxical peripheral vasomotion during REMS supports previous suggestions on severe thermoregulatory impairment during REMS in other species.     

REM sleep deprivation diminishes fear in rats.

To test the hypothesis that REM sleep deprivation decreases fear, the behavior of 44 rats was measured in an open-field test. Prior to this test, the animals were exposed to 4 days to one of four treatments, i.e., either a dry environment control, a wet environment control, a 2-day REM deprivation period, or a 4-day REM deprivation period. During the test both exploration and three parameters of emotionality were recorded. The results offered convincing evidence in support of the hypothesis.     

REM sleep deprivation increases aggressiveness in male rats.

As a test of the hypothesis that REM deprivation increases aggressiveness in rats, the effects of two and four days of REM deprivation were measured on the frequency and latency with which male rats attack mice. The results showed that REM deprivation increased the frequency of attacks, the muricide rate, and the latency to first attack in a “dose-related” fashion. To a degree these behaviors persisted through a 21-day recovery period.     

Acute finger temperature changes preceding sleep onsets over a 45-h period

A resurgence in the field of sleep initiation and thermoregulation has seen a number of investigators reporting relatively gradual increases in distal skin temperatures of the hands and feet prior to sleep onset at typical bedtimes. The present study extends upon prior knowledge by investigating whether: (1) this is a change of distal skin temperature triggered specifically by the attempt to fall asleep and (2) whether this relationship holds for various phases of the circadian rhythm whenever sleep is attempted. Fourteen healthy good sleepers participated in a modified 45-h constant routine (CR) with multiple sleep onset latency tests (MSLT) conducted every half hour. After a brief decrease of finger temperature associated with small postural adjustments at the beginning of each sleep latency test, finger temperature showed rapid (0.8 degrees C min-1) increases of 1-3 degrees C leading up to the onset of sleep. This rapid increase of finger temperature was relatively consistent across the 45-h CR, despite very significant circadian variation of the pre-MSLT baseline finger temperature and homeostatic decrease of sleep latency.     

Swimming immobility of REM sleep deprived rats reared in different environments

This study tested the hypothesis that environmental rearing treatments which alter the REM sleep levels of rats affect swimming immobility, an adaptive, REM sleep sensitive behavior. At weaning, 72 female Sprague-Dawley rats were maintained in either an enriched, an impoverished, or a social control environment for 32–33 days. They were then placed in either a REM sleep depriving platform-in-water condition or in one of two control conditions (large platform or dry control) for 4 days before being scored for swimming immobility during a 10-min swimming test. A 3 (environments) × 3 (platforms) ANOVA revealed a main effect for environments, F(2,63)=5.20, p<0.01. Enriched rats exhibited a behavioral advantage over impoverished rats under the large platform control condition, F(1,63)=6.58, p<0.025, and under the dry control condition, F(1,63)=6.14, p<0.025. However, under the REM depriving condition, their behavioral advantage was virtually eliminated, F(1,63), p<1. The conclusion that the REM sleep levels of the rat groups probably determined their swimming immobility scores is discussed.