Deep Slow Wave Sleep Research Articles

The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat

The effect of a single injection of synthetic delta-sleep-inducing peptide (DSIP, 7 nmol/kg) into the lateral ventricle of 10 cats was investigated by monitoring the sleep-wake cycle during an 8 h period. A significant decrease in sleep latency and a significant increase in total sleep and in total slow wave sleep (SWS) was found following DSIP administration. The increase in sleep resulted exclusively from a significant increase in deep slow wave sleep (S 2), while light slow wave sleep (S 1) was significantly decreased. Neither the total amount of REM sleep, nor hourly values of REM sleep were affected by DSIP application. Additional measures of REM sleep, like REM sleep latency, mean episode number and mean episode length were not different from those found in control conditions. DSIP was immediately effective since the amount of S 2 increased to more than 50% in the first postinjection hour and the difference from the control value was highly significant. The increase in S 2 was maintained over 7 h, and disappeared by the eighth hour. The increase in S 2 was caused by a prolongation of S 2 episodes and not by their more frequent occurrence. The results obtained suggest a sleep-facilitating property of DSIP.

Sleep improvement in dogs after oral administration of mioflazine, a nucleoside transport inhibitor.

Mioflazine, a nucleoside transport inhibitor, was given PO to dogs at doses of 0.04-10 mg/kg. Sixteen hour polygraphic sleep recordings were made and analysis and sleep stage classification was done by computer. Mioflazine decreased wakefulness and increased slow wave sleep, but did not affect the latencies of either REM sleep or slow wave sleep. This increased sleep was due to an increase in the number of light and deep slow wave sleep epochs. The effect lasted for about 8 h. The decreased wakefulness and increased slow wave sleep could be antagonized by the adenosine antagonist caffeine (2.5 and 10 mg/kg, PO); however, there was not a pure antagonistic effect. It might be that the enhancement of slow wave sleep is due to an activation of brain adenosine receptors. This is the first report of a drug acting on adenosine that given orally improves sleep. Mioflazine might be the prototype of substances worth considering for the treatment of a variety of sleep disorders.

Effects of serotonin and noradrenaline uptake blockers on wakefulness and sleep in cats.

The aim of the study was to examine the role of serotonergic (5-HT) and noradrenergic mechanisms in the regulation of wakefulness and sleep. For this purpose, adult cats with implanted electrodes for EEG, EOG and EMG were exposed to the 5-HT uptake blocker citalopram (0.1, 0.5 and 5.0 mg/kg intraperitoneally) and the noradrenaline uptake blocker prindamine (5 mg/kg intraperitoneally) at the start of continuous 16-hour sleep-wake recordings. Citalopram increased deep slow wave sleep and decreased REMS. Also prindamine decreased REMS but initially increased the proportion of time spent in the state of active wakefulness. Furthermore, to examine the interactions between 5-HT-nergic and noradrenergic mechanisms in the regulation of sleep, the administration of citalopram was preceded by intraperitoneal injections of phentolamine (10 mg/kg), an alpha-antagonist, and propranolol (5 mg/kg), a beta-antagonist. Phentolamine was totally ineffective against citalopram whereas propranolol partially counteracted the effects of citalopram on sleep. Prindamine was combined with the alpha-antagonists yohimbine (1 mg/kg), phentolamine (10 mg/kg) and prazosin (1 mg/kg) or with the beta-antagonist propranolol (5 mg/kg). Yohimbine was without any effect on REMS, phentolamine partly antagonized prindamine-induced decrease in the percentage of REMS, and prazosin only prolonged REMS latency and reduced deep SWS as well. Propranolol partially antagonized the prindamine-induced initial increase in active wakefulness time.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological studies of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivatives (450191-S, rilmazafone hydrochloride) (VII). Comparison of sleep-inducing activities between young and elderly rhesus monkeys

The sleep-inducing activities of 450191-S (rilmazafone hydrochloride) were compared among two groups of elderly and one group of young rhesus monkeys, and the relationship between blood levels of five active metabolites of 450191-S and sleep-inducing activities was also examined. Oral administration of 450191-S, 1 mg/kg, caused the quick appearance of slow wave deep sleep (SWDS) and its stable continuity in elderly monkeys, and no significant differences in various sleep parameters were observed among the two groups of eight elderly monkeys. An increase of SWDS was always accompanied by a high blood level of active metabolite M-2. On the other hand, in the young rhesus monkey group, the amount of SWDS and its mean continuity were significantly less, and differences were evident in sleep parameters obtained from a nocturnal 14 hr observation. In conclusion, the difference of sleep-inducing activities between elderly and young monkeys seem to be caused by a difference in the blood level of active metabolites of 450191-S, particularly M-2.

The effect of subcutaneous administration of delta sleep-inducing peptide (DSIP) on some parameters of sleep in the cat

Delta sleep inducing peptide (DSIP) significantly increases deep-slow-wave sleep (DSWS) of cats after subcutaneous (SC) injection. Cats (n=8) were SC injected with DSIP (120 nmol·kg −1) prior to polygraphic recording of EEG combined with electro-oculography, EOG) and electromyography (EMG) for 8 hours. DSIP was found to significantly increase slow-waves (delta sleep) in the sleep EEG. There was a tendency to reduced waking time and a prolongation of slow wave sleep time, and a shortening of sleep onset and REM sleep latencies but the differences from control (Ringer injection) were not statistically significant. There was no change in the amount of REM sleep. These findings support the belief that DSIP can increase sleep wave activity when administered by peripheral route.

Sleep fragmentation in canine narcolepsy.

Genetically narcoleptic dogs were recorded continuously for 24 h to examine their sleep-wake patterns and to evaluate the extent of sleep fragmentation. Three narcoleptic and three control dogs from each of two affected breeds (Labrador retrievers and Doberman pinschers) were surgically implanted with electrodes for recording standard sleep parameters. Recordings were scored in 30-s epochs for the states of active waking, drowsiness, light sleep, deep slow wave sleep, REM sleep, and cataplexy. All affected dogs displayed marked fragmentation and disruption of the sleep-wake cycle characterized by repeated awakenings, frequent shifts in sleep stages, numerous attacks of cataplexy occurring from active waking, and a disturbance of the normal REM-NREM periodicity. This sleep disruption was reflected in significantly greater numbers of episodes of each behavioral state as well as in a 38% increase in the total number of all states. These results demonstrate a severe disturbance of the normal sleep pattern in canine narcoleptics. The possibility of a general dysfunction of circadian organization is discussed.

Electrophysiological evaluation of three paradoxical sleep deprivation techniques in rats

Three different techniques were used to study the effects of 72 hr deprivation of paradoxical sleep on percentages total sleep, light slow wave sleep, deep slow wave sleep and paradoxical sleep during deprivation and recovery periods in rats. The paradoxical sleep deprivation methods used were the classical platform, the pendulum and the multiple platform techniques. The different groups were continuously recorded over a base-line day, three deprivation days and four recovery days. All three groups showed clear suppression of paradoxical sleep throughout the deprivation period, although small differences between the pendulum and the multiple platform technique emerged. The distribution of sleep across the day and the amount of deep slow wave sleep were affected differently. Besides an exception immediately after deprivation, no important differences were detected on the recovery days. The recovery is characterized by an immediate rebound of paradoxical sleep, completed within two days, as well as rapid re-normalization of sleep percentages. A small rebound of deep slow wave sleep was recorded at the end of the dark period during the first three recovery days. Various sleep and non-sleep related variables of the PS deprivation techniques are discussed. It is improbable that the platform-pendulum controversy is due to differences in the amount of PS deprivation or the other sleep parameters measured here. Rather it looks as though non-specific platform effects override the effects of PS deprivation.

Interaction sleep and epilepsy.

In order to improve the diagnosis of epilepsy, a routine EEG recording can be supplemented with a long-lasting sleep recording or with an ambulatory EEG recording. In this paper we compare the all-night polygraphic sleep recording with the 3- to 5-hour recording after 1 night total sleep deprivation, and we discuss the outcome with each. In the first part we have analyzed the relationship between the clinical form of epilepsy and the kind and depth of sleep and we have tried to determine the optimal registration time (in hours) to obtain a maximum diagnostic gain. In the second part we have evaluated the changes in the sleep composition induced by the occurrence of epileptic EEG phenomena and by the intake of antiepileptic drugs. In the third part we have analyzed the changes in the morphological aspects of the epileptic EEG phenomena which can occur under influence of light (NREM 1-2) and deep (NREM 3-4) slow-wave sleep and REM sleep. A sufficient knowledge of these changes is very important to avoid misinterpretations.

Platform sleep deprivation affects deep slow wave sleep in addition to REM sleep

Rats were sleep deprived by the platform method to look for differential effects on light and deep slow wave sleep depending on platform size. Diameters of large and small platforms were 15 cm and 5.1 cm respectively. Sleep was recorded during a baseline light period (09.00–19.00 h), continuously during 48 h of sleep deprivation and during the first lights on recovery period (09.00–19.00 h). In both platform conditions REM sleep was virtually abolished during the first light period (hours 0–10 of sleep deprivation), while NREM sleep was reduced to approximately half of control values. During the second light period (hours 22–34 of sleep deprivation) REM sleep recovered somewhat in the large platform group. Light slow wave sleep (SWS-1) was comparable to baseline while deep slow wave sleep (SWS-2) was still significantly reduced. In the small platform group both SWS-2 and REM sleep was considerably reduced on day 2. Over the whole deprivation period there was an effect of platform size on SWS-1 (higher in the small platform group), and on SWS-2 and REM sleep (lower in the small platform group). During the 9 h light-time recovery sleep there was an REM sleep rebound in both groups. SWS-1 was reduced in both groups while SWS-2 was not significantly increased. The ratio SWS-2 SWS-1 was, however, significantly increased only in the small platform group recovery sleep. The results suggest that platform sleep deprivation deprives the animals of deep slow wave sleep in addition to REM sleep. This has implications for conclusions on REM sleep function based upon REM sleep deprivation.

Prenatal exposure to diazepam results in enduring reductions in brain receptors and deep slow wave sleep

After prenatal exposure to diazepam (Valium), mature rats at 4 months of age displayed slow wave sleep (SWS) electroencephalographic patterns indicating impaired synchronization and SWS mechanisms. These animals spent a much greater portion of their SWS in the lighter SWS I, as compared to the control group which showed a predominance of the deeper SWS II. At one year of age, the diazepam-exposed rats had much fewer diazepam-specific binding sites in the thalamus than the vehicle-exposed controls. These results provide first evidence for a physiological role for benzodiazepine receptors by showing that prenatal exposure to diazepam has an enduring and detrimental effect on their ontogenesis and sleep mechanisms.

Effects of delta sleep inducing peptide on sleep cycle of cats deprived of paradoxical sleep

The effect of synthetic delta sleep inducing peptide (DSIP) on sleep was investigated in cat. DSIP (7 nmol/kg was administered intracerebroventricularly to cats deprived of paradoxical sleep (PS) for 72 h and immediately after termination of PS deprivation an injection of either Ringer or DSIP solution was given. Eight h of recovery sleep was then recorded. DSIP failed to affect the duration of slow-wave sleep, PS and total sleep time. There was, however, significant decrease of wakefulness and light slow-wave sleep (S1) while deep slow-wave sleep (S2) was significantly increased. There was also no change in the latency to the first episode of S2 sleep and PS. Thus, we conclude that DSIP altered the relative amounts of S1 and S2 sleep, causing more S2 (delta) sleep at the time when pressure for sleep was at its highest due to prior sleep deprivation.

An EEG averaging technique for automated sleep-wake stage identification in the rat

An automated on-line sleep-wake classification system based on an averaging technique of the running EEG is described. It operates for three rats simultaneously and is able to discriminate every 5 sec between wakefulness, light slow-wave sleep, deep slow-wave sleep, and paradoxical sleep. The hippocampal EEG and nuchal EMG are used as input parameters. The EEG is bandpass filtered after which a microcomputer samples and averages the filtered EEG and constructs spectrograms. The variability, the theta-delta ratio and the amplitude of the delta waves are obtained from these spectrograms. Together with the amplitude index of the EMG, these three EEG indices are subjected to decision rules for the identification of sleep-wake states. A first evaluation study showed 93% agreement between visual inspection and computer classification. In a second evaluation study 24-hr recordings were made. Clear circadian patterns emerged especially during the light period: deep slow-wave sleep was enhanced during the initial hours, while paradoxical sleep tended to increase over the latter hours. The outcome of these studies is compared with the results obtained with other automated sleep identification procedures.

Hypnotic action of ethyl β-carboline-3-carboxylate, a benzodiazepine receptor antagonist, in cats

The present study demonstrates that ethyl β-carboline-3-carboxylate (β-CCE), a benzodiazepine receptor antagonist, has hypnotic and sedative actions in cats. Moreover, at a dose that does not by itself affect sleep, β-CCE reverses the action of diazepam on sleep organization. The hypnotic effect of subcutaneous administration of β-CCE (5 mg/kg) lasts for 3–4 h. During this period, deep slow wave sleep (deep non-REM sleep) and paradoxical sleep (REM sleep) significantly increase, while wakefulness markedly decreases. These results, which are quite opposite to the effects of benzodiazepines on sleep organization in cats, support the notion that β-CCE also acts as a benzodiazepine antagonist of sleep organization.

The benzodiazepine antagonist, Ro 15-1788, increases REM and slow wave sleep in the dog

The benzodiazepine antagonist, Ro 15-1788, increases REM and deep slow-wave sleep in dogs at a dose of 10 mg/kg orally. These actions are opposite to that of diazepam. This suggests either that Ro 15-1788 possesses hitherto undescribed intrinsic partial inverse agonist activity or that it is antagonizing an endogenous benzodiazepine-like substance which is involved in modulating sleep-wakefulness.

Effects of methoxamine, and alpha-1 adrenoceptor agonist, and prazosin, an alpha-1 antagonist, on the stages of the sleep-waking cycle in the cat.

In these experiments the effects of alpha 1-adrenoceptor agonism and antagonism were studied on the stages of the sleep-waking cycle of the cat, in order to determine optimal levels of alpha 1-adrenergic transmission for these stages. Polygraphic 16-h recordings showed that prazosin, an alpha 1-adrenoceptor antagonist, at 1 mg/kg i.p., increased paradoxical sleep (PS) time from 15.3% to 26.4% (p less than 0.001) of total time, and the number of PS episodes from 30.4 to 43.6 (p less than 0.001). The effect was prompt, reaching a maximum during the first 4 h with a shortening of PS latency from 40.4 min to 11.0 min (p less than 0.001). Prazosin at doses of 0.5 and 3.0 though not at 10.0 mg/kg also slightly, but significantly, increased PS. Methoxamine, and alpha 1-adrenoceptor agonist, at doses of 0.5 and 3.0 mg/kg, increased aroused waking time (low voltage mixed frequency EEG) during the first 4 h from 23.5% to 33.3% (p less than 0.05) and to 50.3% (p less than 0.01), and decreased PS. Prazosin potentiated dose-dependently clonidine-induced drowsiness ( hypersynchronized 4-8 Hz EEG), whereas the decrease in deep slow wave sleep and PS were potentiated only at the largest dose of it. These results indicate that moderate inhibition of cerebral alpha 1-adrenergic transmission facilitates paradoxical sleep in the cat. Furthermore, they suggest that the level of cerebral alpha 1-adrenergic transmission is high during aroused waking and low during drowsy waking.

The effects of adenosine and 2′-deoxycoformycin on sleep and wakefulness in rats

The effects of adenosine (12.5 nmol/rat, i.c.v.) and 2′-deoxycoformycin (2.0 μmol/kg, i.p.) on sleep and wakefulness were examined in rats. Adenosine significantly decreased wakefulness and increased both deep slow-wave sleep and total sleep. 2′-Deoxycorformycin, a potent inhibitor of adenosine deaminase, was administered at a dose which did not produce significant sedative and hypnotic effects, when given alone (although a 4-fold greater dose of this drug has been shown to be hypnogenic in rats) in order to examine the possible potentiation of exogenously administered adenosine. No such potentiation was observed, since treatment with both drugs produced effects qualitatively similar, although not statistically significant, to those of adenosine alone. These data clearly indicate that adenosine is a hypnogenic substance in rats and suggest that these effects may involve adosinergic receptor-mediated modulation of the activity of central adenylate cyclase.

Enregistrement de la ventilation au cours du sommeil par pneumotachographie: inconvenients et avantages

Pneumotachographic recording of ventilation requires an air-tight nasobuccal face-mask which might disturb the subjects' sleep and thereby modify their breathing pattern. In a cross-over randomised study we compared recordings obtained with and without a face-mask in 20 healthy normal volunteers (10 males, 10 females, mean age = 21.7 +/- S.E.M. = 0.5). The sleep modifications that resulted from the presence of the face-mask were a lengthening of the REM-sleep latency (+ 38%; P less than 0.01), an increase in intra-sleep waking-time (+ 65%, P less than 0.05), an increase in stage I duration (+ 40%, P less than 0.02), and a decrease in REM-sleep duration (- 20%, P less than 0.01), resulting in a decrease in total sleep duration (- 9%, P less than 0.05). The sleep latency, the number of awakenings, the stage II duration, the deep slow-wave sleep duration, the sleep stability, and the number of sleep cycles were not significantly modified.

The role of β- and α-adrenoceptors in the regulation of the stages of the sleep-waking cycle in the cat

The effects of β-adrenergic drugs alone and in combination with α-adrenergic drugs on the stages of the sleep-waking cycle were studied in adult cats. Polygraphic sleep recordings of 16 h showed that prenalterol (20 and 40 mg/kg i.p.), a β 1-adrenoceptor-stimulating drug increased paradoxical sleep (PS) in a dose-related manner during 4–12 h. Salbutamol (40 mg/kg), a β 2-adrenoceptor-stimulating drug, decreased PS during the first 4 h. Metoprolol (10 and 50 mg/kg), a relatively selective β 1-adrenoceptor blocking drug, increased drowsy waking during the first 4 h. The larger dose also tended to decrease PS. Already at the lower dose metoprolol partially antagonized the PS increase produced by prazosin, an α 1-adrenoceptor blocking drug. Propranolol (5 mg/kg), a β 1-andβ 2-adrenoceptor blocking drug, which alone decreases PS, antagonized the PS increase induced by phentolamine, an α 1-andα 2-adrenoceptor drug. Atenolol (5 mg/kg), a poorly lipid-soluble β-adrenoceptor blocking drug, failed to counteract phentolamine in increasing PS. Metoprolol (10 and 50 mg/kg) and propranolol (5 mg/kg) clearly potentiated the increase in drowsy waking and decrease in deep slow wave sleep and PS induced by clonidine (0.01 mg/kg), an α 2-adrenoceptor-stimulating drug. The results support the involvement of β-adrenoceptors in the regulation of the sleep-waking cycle. A high level of β-adrenergic activity may facilitate the production of PS. A low level of β-adrenergic activity, especially in combination with a high level of α 2-adrenergic activity, may facilitate the production of drowsy waking. Central α 1-andβ 1-adrenoceptors may mediate opposite functions in the regulation of PS.

Hypnotic effects of deoxycorformycin in rats

Rats implanted with EEG and EMG electrodes were treated with deoxycoformycin (0.5 or 2.0 mg/kg, i.p.), and polygraphically recorded for 6 h. Deoxycoformycin is a potent inhibitor of adenosine deaminase and would be expected to elevate the levels of adenosine in the central nervous system. The 0.5 mg/kg dose of the drug increased REM sleep and reduced REM sleep latency while the dose of 2.0 mg/kg increased deep slow-wave sleep (S 2). These results appear to be consistent with those reported previously for the adenosine analog, N 6-( l-phenylisopropyl)-adenosine (L-PIA) and indicate a hypnotic role for adenosine.

Serotonergic mechanisms and sleep rebound

The administration of p-chlorophenylalanine (PCPA), an inhibitor of serotonin (5-HT) biosynthesis, at the end of a 48 h sleep deprivation does not impair the subsequent rebound of deep slow wave sleep (SWS2) and paradoxical sleep (PS). On the contrary, the administration of PCPA during a 48 h sleep deprivation is followed by a great decrease of light slow wave sleep (SWS1) and by total disappearance of SWS2 while some rebound of PS still occurs in narcoleptic-like attacks. These experiments provide evidence that sleep inducing materials are accumulated during sleep deprivation. Serotonergic processes appear to be involved in the regulatory mechanisms of the biosynthesis and the accumulation of SWS2 and PS factors.