Duration Of Rapid Eye Movement Sleep Episodes Research Articles

Fluoxetine, but not paroxetine, alters the jaw-closing muscle activity during non-rapid eye movement sleep in mice

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24 h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6 h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00–08:00 and 08:00–14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

A probabilistic model for the ultradian timing of REM sleep in mice.

A salient feature of mammalian sleep is the alternation between rapid eye movement (REM) and non-REM (NREM) sleep. However, how these two sleep stages influence each other and thereby regulate the timing of REM sleep episodes is still largely unresolved. Here, we developed a statistical model that specifies the relationship between REM and subsequent NREM sleep to quantify how REM sleep affects the following NREM sleep duration and its electrophysiological features in mice. We show that a lognormal mixture model well describes how the preceding REM sleep duration influences the amount of NREM sleep till the next REM sleep episode. The model supports the existence of two different types of sleep cycles: Short cycles form closely interspaced sequences of REM sleep episodes, whereas during long cycles, REM sleep is first followed by an interval of NREM sleep during which transitions to REM sleep are extremely unlikely. This refractory period is characterized by low power in the theta and sigma range of the electroencephalogram (EEG), low spindle rate and frequent microarousals, and its duration proportionally increases with the preceding REM sleep duration. Using our model, we estimated the propensity for REM sleep at the transition from NREM to REM sleep and found that entering REM sleep with higher propensity resulted in longer REM sleep episodes with reduced EEG power. Compared with the light phase, the buildup of REM sleep propensity was slower during the dark phase. Our data-driven modeling approach uncovered basic principles underlying the timing and duration of REM sleep episodes in mice and provides a flexible framework to describe the ultradian regulation of REM sleep in health and disease.

Sleep in ostrich chicks (Struthio camelus).

It has been reported that adult ostriches displayed the longest episodes of rapid eye movement (REM) sleep (up to 5 min) and more REM sleep (24% of the nighttime) than any other bird species. If the mammalian ontogenetic trend exists in the ostrich, then the amounts of REM and the duration of sleep episodes in young ostriches may be greater than those reported in adults. We investigated sleep in 1.5-3.5 month old ostrich chicks. Recordings were conducted during nighttime (20:00-08:00), the main sleep period in ostriches, which are diurnal. The polygrams were scored in 4-s epochs for waking, non-rapid eye movement (NREM) sleep and REM sleep, as in other bird studies. REM sleep in ostrich chicks occurred during both cortical EEG activation and during slow waves, as was described in adult ostriches. The chicks spent 69.3% ± 1.5% of the night in NREM sleep. REM sleep occupied 14.1% ± 1.8% of the night or 16.8% ± 2.0% of nighttime sleep. Episodes of REM sleep lasted on average 10 ± 1 s and ranged between 4 and 40 s. Therefore, the total amount and duration of REM sleep episodes in ostrich chicks were substantially smaller than reported in adult ostriches while the amounts of NREM sleep did not greatly differ. The developmental profile of REM sleep ontogenesis in the ostrich may be remarkably different from what has been reported in all studied mammals and birds.

Sociality Affects REM Sleep Episode Duration Under Controlled Laboratory Conditions in the Rock Hyrax, Procavia capensis.

The rock hyrax, Procavia capensis, is a highly social, diurnal mammal. In the current study several physiologically measurable parameters of sleep, as well as the accompanying behavior, were recorded continuously from five rock hyraxes, for 72 h under solitary (experimental animal alone in the recording chamber), and social conditions (experimental animal with 1 or 2 additional, non-implanted animals in the recording chamber). The results revealed no significant differences between solitary and social conditions for total sleep times, number of episodes, episode duration or slow wave activity (SWA) for all states examined. The only significant difference observed between social and solitary conditions was the average duration of rapid eye movement (REM) sleep episodes. REM sleep episode duration was on average 20 s and 40 s longer under social conditions daily and during the dark period, respectively. It is hypothesized that the increase in REM sleep episode duration under social conditions could possibly be attributed to improved thermoregulation strategies, however considering the limited sample size and design of the current study further investigations are needed to confirm this finding. Whether the conclusions and the observations made in this study can be generalized to all naturally socially sleeping mammals remains an open question.

Developmental Changes in Ultradian Sleep Cycles across Early Childhood.

Nocturnal human sleep is composed of cycles between rapid eye movement (REM) sleep and non-REM (NREM) sleep. In adults, the structure of ultradian cycles between NREM and REM sleep is well characterized; however, less is known about the developmental trajectories of ultradian sleep cycles across early childhood. Cross-sectional studies indicate that the rapid ultradian cycling of active-quiet sleep in infancy shifts to a more adult-like pattern of NREM-REM sleep cycling by the school-age years, yet longitudinal studies elucidating the details of this transition are scarce. To address this gap, we examined ultradian cycling during nocturnal sleep following 13 h of prior wakefulness in 8 healthy children at 3 longitudinal points: 2Y (2.5-3.0 years of age), 3Y (3.5-4.0 years of age), and 5Y (5.5-6.0 years of age). We found that the length of ultradian cycles increased with age as a result of increased NREM sleep episode duration. In addition, we observed a significant decrease in the number of NREM sleep episodes as well as a nonsignificant trend for a decrease in the number of cycles with increasing age. Together, these findings suggest a concurrent change in which cycle duration increases and the number of cycles decreases across development. We also found that, consistent with data from adolescents and adults, the duration of NREM sleep episodes decreased with time since lights-off whereas the duration of REM sleep episodes increased over this time period. These results indicate the presence of circadian modulation of nocturnal sleep in preschool children. In addition to characterizing changes in ultradian cycling in healthy children ages 2 to 5 years, this work describes a developmental model that may provide insights into the emergence of normal adult REM sleep regulatory circuitry as well as potential trajectories of dysregulated ultradian cycles such as those associated with affective disorders.

Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

Optogenetic and pharmacogenetic probing of rapid eye movement (REM) sleep circuitry

Introduction Rapid eye movement (REM) sleep is characterized by the activation of cortical electroencephalogram (EEG) and loss of muscle tone (atonia). The exact neuronal circuit mediating the generation and timing of this state is not fully understood. The subcoeruleus (Sub-C) neurons are hypothesized to generate REM sleep and its characteristics. Here we aimed to determine how optogenetics and pharmacogenetic stimulation impacts REM sleep expression. Materials and methods Study#1: To precisely control the neuronal activity of the Sub-C region, we bilaterally infused 200 nL of an adeno-associated viral vector (AAV) containing a light-sensitive opsin (AAV-hsyn- hChR2(H134R)-eYFP) virus into the Sub-C of 4 mice. Animals were instrumented for EEG and EMG recordings. Neurons were stimulated with short blue light pulses (5 ms) at 1 and 10 Hz either independently of behavioral state or specifically during REM sleep. Study#2: To stimulate the Sub-C population for longer time periods, we bilaterally microinjected 400 nL of an AAV harboring a modified muscarinic G-protein coupled receptor (AAV-HSYN-HA-hm3D(Gq)- IRES-mCitrine) into the Sub-C of 3 mice. Administration of clozapine-N-oxide (CNO, 5 mg/kg) activated neurons in the Sub-C. Only animals that had histological verification of ChR2 and hm3D(Gq) receptor expression in the Sub-C region were used for analysis. Results We found that semi-chronic bilateral light activation of Sub-C neurons at 10 Hz, but not 1 Hz, triggered REM sleep-like EEG activity (theta, 4–8 Hz) during light stimulation, and increased EEG Theta power by 64 ± 16% compared to baseline. Under some conditions, light stimulation prolonged the duration of REM sleep episodes by almost 2-fold. Pharmacogenetic manipulation of the neurons in the Sub-C caused a change in behavioural phenotype where the distribution of EEG frequencies shifted towards a REM sleep-like pattern (theta, 4–8 Hz) independent of the behavioural state. Moreover, the average duration of REM sleep-like periods were greater than REM sleep periods under control condition (i.e., saline). Conclusion These results support the hypothesis that the Sub-C region is involved in controlling REM sleep and its associated phenomena. Acknowledgements This research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) , the Canadian Institutes of Health Research (CIHR) and the CIHR Sleep and Biological Rhythms Toronto .

Absence of systematic relationships between REMS duration episodes and spectral power Delta and Ultra-Slow bands in contiguous NREMS episodes in healthy humans

Previous studies in animals and humans have reported correlations between the durations of rapid eye movement sleep (REMS) episodes and immediately preceding or subsequent non-REMS (NREMS) episodes. The relationship between these two types of sleep is a crucial component in understanding the regulation and neurophysiology of ultradian alternations that occur during sleep. Although the present study replicated previous studies, we also measured NREMS in terms of spectral power Delta and Ultra-Slow bands in addition to duration in examining correlations. The spectral power Delta band, also known as slow-wave activity, measures sleep quantity and is believed to reflect sleep physiology better than mere episode durations. The Ultra-Slow spectral power band was analyzed in parallel. Healthy human participants of both sexes (n = 26, age range 15-45 yr, n = 12 female) were carefully selected to participate in two consecutive series of home polysomnograms performed after 2 nights of habituation to the equipment. In the analyses, REMS episode durations (minutes) were compared with immediately preceding and immediately subsequent NREMS episodes (Delta and Ultra-Slow power) in each sleep cycle. REMS episode duration was more strongly correlated with preceding NREMS episodes than with subsequent NREMS episodes. However, in most cases, no correlations were observed in either direction. One ultradian sleep regulation hypothesis, which is based on stronger correlations between REMS and subsequent NREMS episode durations, holds that the main purpose of REMS is to reactivate NREMS during each sleep cycle. The present results do not support that hypothesis.

Small platform sleep deprivation selectively increases the average duration of rapid eye movement sleep episodes during sleep rebound

The single platform-on-water (flower pot) method is extensively used for depriving rapid eye movement sleep (REMS). Detailed comparison of sleep–wake architecture, recorded during the rebound period after spending three days on either a small or large platform, could separate the effects of REMS deficit from other stress factors caused by the procedure. A further aim of the study was to find the most characteristic REMS parameter of the rebound originating from REMS deficit. Rats were kept on a small or large platform for 72 h. Their fronto-parietal electroencephalogram, electromyogram and motility were recorded during the 24 h rebound at the beginning of the passive phase. A similar period of a home cage group was also recorded. The most typical differences between the two rebound groups were the increased cumulative time and longer average duration of REMS episodes without significant change in the number of these episodes of the small platform animals during the passive phase. Results obtained by cosinor analysis were in accordance with the findings above. Since we did not find any difference in the average duration of REMS episodes comparing the large platform rebound group and the home cage group, we concluded that the increased mean duration of REMS episodes is a selective marker for the rebound caused by small platform sleep deprivation, while other changes in sleep architecture may be the consequence of stress and also some sleep deficit.

Differential effects of psychological and physical stress on the sleep pattern in rats.

In the present study, we investigated the acute effects of 2 different kinds of stress, namely physical stress (foot shock) and psychological stress (non-foot shock) induced by the communication box method, on the sleep patterns of rats. The sleep patterns were recorded for 6 h immediately after 1 h of stress. Physical and psychological stress had almost opposite effects on the sleep patterns: In the physical stress group, hourly total rapid eye movement (REM) sleep and total non-REM sleep were significantly inhibited, whereas psychological stress enhanced hourly total REM sleep but not total non-REM sleep. Further results showed that total REM sleep, total non-REM sleep, total sleep and the total number of REM sleep episodes in 5 h were reduced, and that sleep latency was prolonged compared to the control group. On the other hand, in the psychological stress group, the total REM sleep in 5 h was increased significantly due to the prolongation of the average duration of REM sleep episodes and reduced REM sleep latency. In addition, the plasma of corticosterone increased significantly after physical stress but not after psychological stress. These results suggested that the sleep patterns, particularly the patterns of REM sleep following physical and psychological stress, are probably regulated by 2 different pathways.

Iron deficiency anemia in infancy is associated with altered temporal organization of sleep states in childhood.

The highest prevalence of iron deficiency anemia (IDA) in infancy coincides with a time of rapid changes in sleep organization. Since IDA in infancy is associated with long-lasting neurofunctional effects despite iron treatment, the normal development of sleep patterns might be affected. Night polysomnographic recordings were performed in 55 healthy 4-y-old children (former IDA = 27, nonanemic controls = 28). Both groups were followed from infancy and were similar in background characteristics. The duration of each waking episode was measured, as was the duration of each episode of nonrapid eye movement (NREM) sleep stages 1 (NREM1), 2 (NREM2), and 3-4 (SWS), and rapid eye movement (REM) sleep. The data were analyzed according to the successive thirds of the total sleep time (TST). Relative to controls, former IDA children showed: a) longer duration of REM sleep episodes in the first third and shorter in the last third; b) more REM sleep episodes in the first third and fewer in the second third; and c) shorter latency to the first REM sleep episode and shorter NREM stage 2 and SWS episodes within the first sleep cycle. The results show that early IDA is associated with long-lasting alterations in the temporal organization of sleep patterns.

Short light–dark cycles affect sleep in mice

Environmental light has a strong impact on human physiology and behaviour, including cognitive functioning and alertness. Previous studies have shown that short light-dark (LD) cycles influence sleep in the albino rat. Rapid eye movement (REM) sleep increases after the onset of darkness and increases after light onset. In the present study, we investigated whether light affects sleep in mice. To this purpose the electroencephalogram and electromyogram of nine adult male C57BL/6 mice was recorded under 12 : 12 h baseline LD conditions, followed by 24 h continuous darkness (DD) and 6 days with LD cycles of different durations (2 h, 30 min, 14 min, 10 min, 4 min and 2 min), presented in a randomized order. NREM sleep was evenly distributed over the light and dark intervals of all short LD cycles. REM sleep, however, was increased during the dark intervals of short (10-30 min) LD cycles. Analysis showed that in these LD cycles, the increment in REM sleep was maximal in the second minute after dark onset, where the percentage of epochs with REM sleep increased significantly to 175% of baseline values. This increase was attributable to an increase in REM sleep episode duration. The recorded responses show that sleep in mice is affected by photic stimulation. The results demonstrate that pigmented animals can show REM sleep induction after dark onset and indicate that light has significant effects on the regulation of sleep.

The effects of atropine on changes in the sleep patterns induced by psychological stress in rats

The present study was designed to investigate the acute effects of psychological stress on the sleep patterns of rats and the potential mechanisms underlying these effects. Psychological stress was induced using a communication box. In a preliminary study, sleep recording was performed for 6 h immediately after 1-h stress in rats. The results showed that psychological stress significantly enhanced the total amount of rapid eye movement (REM) sleep by prolonging the average duration of REM sleep episodes during first 3 h of sleep, whereas the total amount of non-rapid eye movement sleep was not influenced. In a second study, three doses of atropine (3, 10, or 30 nmol) were intracerebroventricularly microinjected into the rats. Total REM sleep was inhibited by the highest dose of atropine during the first 3 h of sleep in the stressed group but not in the control group; the inhibition of total REM sleep was due to a reduction in the average duration of REM sleep episodes. These results suggest that the increase in total REM sleep induced by stress was related to the activation of cholinergic neurons. In addition, plasma corticosterone—an index of hypothalamic–pituitary–adrenal (HPA) axis activity in response to stress—was examined after psychological stress. The concentration of corticosterone did not change significantly. Therefore, the abnormal sleep patterns could not be simply attributed to the HPA axis. These results indicate that the changes in sleep patterns induced by stress were related to cholinergic neurons, but not the HPA axis.

Beta2-containing nicotinic receptors contribute to the organization of sleep and regulate putative micro-arousals in mice.

The cholinergic system is involved in arousal and in rapid eye movement sleep (REMS). To evaluate the contribution of nicotinic acetylcholine receptors (nAChRs) to these functions, we studied with polygraphic recordings the regulation of sleep in mice lacking the beta2 subunit gene of the nAChRs, a major component of high-affinity nicotine binding sites in the brain. Nicotine (1-2 mg/kg, i.p.) increased wakefulness in wild-type but not knock-out animals, indicating that beta2-containing nAChRs mediate the arousing properties of nicotine. Under normal conditions, the beta2-/- mice displayed the same amounts of waking, non-REM sleep (NREMS) and REMS as their wild-type counterparts. However, they exhibited longer REMS episodes and a reduced fragmentation of NREMS by events characterized notably by a transient drop in EEG power and frequently associated with EMG activation, tentatively referred to as micro-arousals. Respiration monitoring showed that these events were accompanied with, but not caused by, breathing irregularities. Sleep deprivation of beta2-/- mice resulted in a normal increase in REMS episode duration and NREMS delta power but yielded a reduction of the number of micro-arousals in NREMS. In contrast, in beta2-/- mice, a 1 hr immobilization stress failed to produce the normal rebound in REMS in the following 12 hr and, instead, was associated with increased NREMS fragmentation and sustained corticosterone levels. Our results show that the beta2-containing nAChRs contribute to the organization of sleep by regulating the transient phasic activity in NREMS, the REMS onset and duration, and the REMS-promoting effect of stress.

Effect of chronic treatment with milnacipran on sleep architecture in rats compared with paroxetine and imipramine

A number of studies in humans and various other species have shown that chronic treatment with antidepressants, such as tricyclics or selective serotonin reuptake inhibitors (SSRIs), induces a decrease or suppression of rapid eye movement (REM) sleep. The effect of a new selective serotonin and noradrenaline reuptake inhibiting (SNRI) antidepressant, milnacipran, on REM sleep has been investigated and compared with that of the SSRI, paroxetine, and the tricyclic, imipramine. Rats injected with vehicle or milnacipran twice a day showed, over 24 h, a similar amount of REM sleep, number and duration of REM sleep episodes to control rats. In contrast, rats treated acutely with imipramine or paroxetine showed a statistically significant decrease in the total quantity of REM sleep. The number of REM sleep episodes was decreased while their duration was increased. A more detailed analysis showed further that the quantity of REM sleep was decreased for the first 4 h following the 9 a.m. injection but not the 7 p.m. injection for milnacipran, during the first 6 h for paroxetine and for the entire light–dark period for imipramine. For all drugs, the quantities of slow-wave sleep and waking over 24 h were not significantly different from control conditions and no rebound of REM sleep occurred during the day following withdrawal. Power spectrum analysis revealed no global changes in the different electroencephalogram (EEG) waves (delta, theta, gamma) between the control condition and the different treatments during waking, slow-wave sleep or REM sleep. Taken together our results indicate that the SNRI, milnacipran, at therapeutic doses, induces only minor disturbances of REM sleep compared with a SSRI and tricyclic antidepressant used. Possible mechanisms responsible for the difference of action on REM sleep of milnacipran are discussed.

Carbachol models of REM sleep: recent developments and new directions.

Since the early '60s, injections of a broad-spectrum muscarinic cholinergic agonist, carbachol, into the medial pontine reticular formation (mPRF) of cats have been extensively used as a tool with which to study the neural mechanisms of rapid eye movement (REM) sleep. During the last decade, new carbachol models of REM sleep were introduced, including chronically instrumented/behaving rats and "reduced" preparations such as decerebrate or anesthetized cats and rats. The combined results from these distinct models show interspecies similarities and differences. The dual nature, both REM sleep-promoting and wakefulness (or arousal)-promoting, of the cholinergic effects exerted within the mPRF is more strongly expressed in rats than in cats. This strengthens the possibility suggested by earlier central neuronal recordings that active wakefulness and REM sleep have extensive common neuronal substrates, and may have evolved from a common behavioral state. Carbachol studies using different intact and reduced models also suggest that powerful REM sleep episode-terminating effects originate in suprapontine structures. In contrast, the timing of REM sleep-like episodes in decerebrate models is determined by a pontomedullary neuronal network responsible for the generation of an ultradian cycle similar to the basic rest-activity cycle of N. Kleitman. Other presumed species differences, such as the more widespread distribution of carbachol-sensitive sites or the relative failure of carbachol to increase the duration of REM sleep episodes in rats when compared to cats, may be of a quantitative or technical nature. While carbachol and many other neurotransmitters and peptides microinjected into the mPRF evoke, enhance or suppress REM sleep, the most sensitive site(s) of their actions have not been fully mapped, and the nature of the cellular and neurochemical interactions taking place at the sites where carbachol triggers the REM sleep-like state remain largely unknown. Similarly, little is known about the pathways between the mPRF and medial medullary reticular formation, but the existing evidence suggests that they are reciprocal and essential for the generation of both natural and carbachol-induced REM sleep. Studies of the mesopontine cholinergic neurons, which are hypothesized to be the main source of endogenous acetylcholine for the mPRF, need to be extended to neurons of the mPRF and cells located functionally downstream from this important site for REM sleep, or both REM sleep and active wakefulness.

Changes in REM sleep occurrence due to rhythmical auditory stimulation in the rat

The effects of the rhythmical delivery of an auditory stimulus (1000 Hz, from 50 to 100 dB, 20 ms, every 20 s) on the pattern of rapid eye movement (REM) sleep occurrence was studied in the rat. The stimulation was simultaneously carried out on pairs of rats over 5 consecutive days (10-h recording sessions), during which a tone of increasing intensity (50, 63, 75, 88, 100 dB) was used. In each experimental session, auditory stimulation was triggered by the REM sleep occurrence of one rat (REMS-selective stimulation) whilst the other rat simultaneously received the same stimuli, but during any stage of the wake–sleep cycle (REMS-unselective stimulation). The results showed that the total amount of REM sleep in the 10-h recording session was increased over the 5 days of stimulation in the REMS-unselective group. This effect was due to an increase in the mean duration of REM sleep episodes. However, no significant changes were observed in animals under REMS-selective stimulation, nor in a third group of animals in which the spontaneous evolution of REM sleep occurrence (REMS-spontaneous) was studied. Since 86% of the stimuli under the REMS-unselective auditory stimulation fell outside REM sleep, the result would suggest that REM sleep occurrence is affected when the stimuli are delivered during a time period (i.e. during wakefulness or non-REM sleep) in which it is well known that physiological regulations are fully operant.

Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes.

Substances acting upon rapid eye movement (REM) sleep or paradoxical sleep (PS) can affect the number and/or the duration of PS episodes. In the present study, we investigated the effects of the proopiomelanocortin-derived peptide CLIP (corticotropin-like intermediate lobe peptide, ACTH 18-39) and its N-terminal fragments ACTH 18-24 and ACTH 20-24 on the duration of PS episodes in rats. Intracerebroventricular injection of ACTH 20-24 caused a pronounced prolongation of PS episodes (up to 7 min duration, never seen under baseline conditions), whereas ACTH 18-24 acted in a similar way but without reaching statistical significance. We suggest that short N-terminal CLIP fragment(s) may represent endogenous hypnogenic factor(s) involved in the regulation of paradoxical sleep.

Arousal-enhancing properties of the CB1 cannabinoid receptor antagonist SR 141716A in rats as assessed by electroencephalographic spectral and sleep-waking cycle analysis

The effects of the central (CB1) cannabinoid receptor antagonist SR 141716A on the sleep-waking cycle were investigated in freely-moving rats using time scoring and power spectral analysis of the electroencephalogram (EEG). Over a 4-hour recording period, SR 141716A (0.1, 0.3, 1, 3 and 10 mg/kg I.P.) dose-dependently increased the time spent in wakefulness at the expense of slow-wave sleep (SWS) and rapid eye movement sleep (REMS), delayed the occurrence of REMS but did not change the mean duration of REMS episodes. Moreover, the compound induced no change in motor behavior. At the efficient dose of 3 mg/kg I.P., SR 141716A reduced the spectral power of the EEG signals typical of SWS but did not affect those of wakefulness. Taken together, these results demonstrate that the EEG effects of SR 141716A reflect arousal-enhancing properties. In addition, the present study suggests that an endogenous cannabinoid-like system is involved in the control of the sleep-waking cycle.

REM sleep inhibition by desipramine: evidence for an α-1 adrenergic mechanism

The acute administration of drugs that block norepinephrine (NE) reuptake suppresses rapid eye movement (REM) sleep in cats and other mammals. The mechanism is presumed to involve NE acting on cells in a pontine REM sleep-generator region. Postsynaptic noradrenergic receptor mechanisms have not been identified. In the present experiments, we tested the ability of the α-1 antagonist prazosin and the beta antagonist propranolol to reverse the REM sleep suppression produced by the NE reuptake blocker desipramine (DMI) in the cat. DMI reduced the number of REM sleep episodes, the REM percentage (REM sleep time/total sleep time), and the average REM sleep episode duration. The co-administration of prazosin, but not propranolol, increased the REM percentage and the average REM sleep episode duration toward the placebo level. The co-administration of the peripherally-acting, anti-hypertensive agent hydralazine did not reverse the DMI-induced REM sleep suppression. While the identity of the brain region(s) involved in mediating the α-1 noradrenergic suppression of REM sleep by DMI remains unclear, there is reason to consider forebrain structures including the amygdala as well as the pontine areas that generally have been implicated in REM sleep control.