Decrease In Paradoxical Sleep Research Articles

Glutamate microinjection in the medial septum of rats decreases paradoxical sleep and increases slow wave sleep

The role of the medial septum in suppressing paradoxical sleep and promoting slow wave sleep was suggested on the basis of neurotoxic lesion studies. However, these conclusions need to be substantiated with further experiments, including chemical stimulation studies. In this report, the medial septum was stimulated in adult male rats by microinjection of L-glutamate. Sleep-wakefulness was electrophysiologically recorded, through chronically implanted electrodes, for 2 h before the injection and 4 h after the injection. There was a decrease in paradoxical sleep during the first hour and an increase in slow wave sleep during the second hour after the injection. The present findings not only supported the lesion studies but also showed that the major role of the medial septum is to suppress paradoxical sleep.

Neuroimmune response and sleep studies after whole body irradiation with high-LET particles

In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42–76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuroimmune response, evaluated by interleukin-1 (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight.

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

Ozone (O 3) 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 O 3 exposure to 0.5 ppm. Polygraphic sleep records were taken simultaneously to neurochemical sampling. O 3 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, O 3 exposure decreased the PS by 65% (Mann–Whitney's U-test, p ≤ 0.0003) and a concomitant decrease of extracellular Ach of 58% ( p ≤ 0.0239) was observed during the light phase. These changes were maintained during the dark phase, although it was also observed that slow-wave sleep increased by 75% ( p ≤ 0.0013) while wakefulness was decreased in 35% ( p ≤ 0.0007). We conclude that Ach release in MPO follows a circadian rhythm that is disrupted by O 3 exposure, and these changes are strongly associated with the O 3-induced PS disruptions.

Effects of Maternal Separation on Baseline Sleep and Cold Stress-Induced Sleep Rebound in Adult Wistar Rats

To evaluate the influence of early life environments on basal and cold stress-induced sleep patterns in rats. The design was a 3 (Groups [control, early handling, maternal separation]) x 2 (Situations [basal, poststress]) x 11 (Time-blocks) factorial design. From postnatal days 2 to 14, whole litters were either submitted to early handling (15 minutes per day away from the mother) or maternal separation (180 minutes per day away from the mother). At 75 to 90 days of age, sleep was recorded for 22 hours (beginning at 9:00 AM) before and after 1 hour of cold stress (4 degrees C). Wistar male rats (n = 7-10 animals per group). Sleep was analyzed in blocks of 2 hours, in 30-second epochs, separately in the daytime and nighttime sleep recordings. Maternally separated rats exhibited more paradoxical sleep at baseline, compared to both control and early-handled rats. In the first 2 hours following the end of cold stress, all groups showed a decrease in paradoxical sleep, whereas slow-wave sleep was reduced only in the control group. The highest corticosterone plasma concentration was observed immediately after stress. Sleep rebound after stress was equally manifested in all groups in the dark part of the light-dark cycle. Maternal separation during early infancy resulted in permanent changes of the sleep architecture reflected by augmented time spent in paradoxical sleep. Although these findings were not expected in light of the literature, they emphasize the importance of the early familiar environment on future behavior of rats.

Critical role for M3 muscarinic receptors in paradoxical sleep generation in the cat.

In the cat, microdialysis application of 200 microM carbachol to the peri-locus coeruleus alpha (peri-LC alpha) of the mediodorsal pontine tegmentum produced a marked (< or = 5-fold) increase in paradoxical sleep. This effect was blocked by 5-50 microM 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), an M1/M3-selective muscarinic receptor antagonist. In contrast, the effect was not reversed by methoctramine, an M2-selective antagonist, or pirenzepine, an M1-selective antagonist, even at concentrations as high as 500 microM. In addition, unilateral application of 5 microM 4-DAMP alone to the peri-LC alpha induced both a > 60% decrease in paradoxical sleep and a state of paradoxical sleep without atonia, whereas 50 microM pirenzepine and 500 microM methoctramine had no effect. Our findings are further evidence for the important role played by the peri-LC alpha and demonstrate a critical role for M3 muscarinic cholinergic receptors in the generation of paradoxical sleep.

The effects of ozone exposure on the sleep-wake cycle and serotonin contents in the pons of the rat

Polysomnographic studies were done at hourly intervals during 0.00, 0.35, 0.75 and 1.50 ppm of ozone (O 3) exposure. We found a significant decrease in paradoxical sleep after 2 h and an increase in slow wave sleep after 12 h at all concentrations of O 3. High resolution liquid chromatography demonstrated an increase in 5-HT concentration in the rat pons, in a roughly stepwise fashion as the O 3 concentration increased. We propose that reaction products derived from O 3 exposure, such as prostaglandins, could be affecting those physiological and biochemical mechanisms critical for the generation and maintenance of the sleep-wake cycle.

Effects of moclobemide on sleep in healthy human subjects

Ten healthy, normal subjects (5 male and 5 female) aged 20-28 years participated in this experimental study of the effect of moclobemide on sleep. The design consisted of 2 sessions of 5 nights each, comprising 1 adaptation night, 2 nights on placebo and 2 inputs of moclobemide 4 mg/kg (session B). The 2 sessions were separated by at least 15 days and their order was balanced and randomized. During the last 4 nights of each session, sleep parameters were recorded throughout the night according to standard procedures. Moclobemide at a dose of 4 mg/kg induced moderate changes in the sleep-wake balance: a significant increase in stage 1 on the second drug night, a slight increase in stage 2 and a significant decrease in paradoxical sleep on the 2 drug nights. There was also a moderate reduction in the number of rapid eye movements (REM) during paradoxical sleep, but the number of cycles and latency to paradoxical sleep were unchanged, as well as all other sleep parameters measured. With 6.5 mg/kg, the changes were more pronounced: total sleep time was diminished, but this was significant only on the second and third nights. Transient awakenings increased significantly on the first drug night, and wakening latency decreased. The only modification of orthodox sleep was an increase in the percentage of stage 2 on the first drug night, whereas slow-wave sleep was unchanged. Paradoxical sleep was reduced on the first 2 drug nights, but tolerance appeared on the third night. The decrease in paradoxical sleep was exacerbated in the last part of the night. REM were decreased during paradoxical sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Melatonin modulates the sensitivity of 5-hydroxytryptamine-2 receptor-mediated sleep—wakefulness regulation in the rat

The interaction between melatonin and two 5-hydroxytryptamine (5-HT 2) compounds was studied on sleep patterns in rats. Administration of the 5-HT 2 receptor antagonist ritanserin (0.63 mg/kg, i.p.) resulted in a significant increase of deep slow wave sleep (SWS2) and a decrease of paradoxical sleep (PS). The 5-HT 2 receptor agonist DOM (1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane) (0.63 mg/kg, i.p.) produced a significant reduction of both SWS2 and PS. Melatonin (1 mg/kg, i.p.) alone did not alter sleep but counteracted the sleep effects induced by ritanserin as well as DOM. It is proposed that melatonin modulates the sensitivity of 5-HT 2 receptor-mediated sleep response probably by an indirect route.

Effects of hypophysectomy on the sleep of neonatally Monosodium Glutamate-treated rats

Monosodium Glutamate (MSG), known to induce neuronal cell degeneration of the arcuate nucleus of the hypothalamus, was subcutaneously injected (4 mg/g body wt.) at postnatal days 1 to 5 or 1 to 10 in female rats. Hypophysectomy was performed at 45–60 days of age. Sleep parameters were continuously recorded for at least 7 days. Results indicated that hypophysectomized (HYPX) NaCl-treated rats showed an increase of Slow Wave Sleep (SWS) (+29.6%) and a decrease of Paradoxical Sleep (PS) (−36.7%) durations. In MSG-treated rats, hypophysectomy did not alter SWS durations but it increased PS durations as MSG dosing increased. It was concluded that arcuate nucleus neurons seemed to be not critically involved in sleep production mechanisms.

Changes in the rat sleep-wake cycle produced by d,l-β-(1-naphthyl)alanine, a tryptophan analog

The effects of i.p. injections of d,l-β-(1-naphthyl)alanine, a synthetic analog of tryptophan were tested on the rat sleep-waking cycle. Administration of 30, 60 and 120 mg/kg resulted in a significant increase in slow-wave sleep (SWS) and a decrease in paradoxical sleep (PS). These modifications were dose-dependent. These results were compared with those previously obtained with l-tryptophan and several analogs and discussed in relation with possible changes in central serotonergic activity.

Hypophysectomy in monosodium glutamate-pretreated rats suppresses paradoxical sleep rebound

Control untreated and pretreated female rats at birth with 10 injections of monosodium glutamate (MSG, 4 mg/g b. wt.) were hypophysectomized (HYPX) at 45–60 days of age and their sleep-waking cycle continuously registred. In control rats, hypophysectomy was followed by a 35.7% decrease in paradoxical sleep (PS) duration while it has no effect on the sleep of MSG-treated rats. After 24 h of PS deprivation, there was a normal immediate rebound of PS in the control HYPX and MSG rats while there was no significant rebound in the HYPX-MSG-treated rats. It is concluded that neuropeptides from arcuate nucleus and hypophysis are involved in a PS rebound mechanism.

Paradoxical sleep and coping with environmental change

Long-term sleep recordings of mice from 3 inbred strains showed that the amount of time spent in sleep over successive 24-h periods varied as the subjects adapted to experimental conditions. A sinusoidal type variation, with a period of about 15 days, modulating the basic trends in sleep times is described; but the principal finding of this study relates to a monotonic decrease in Paradoxical Sleep (PS) as recording continued. Age, stimulus deprivation and fatigue effects do not appear to be causative factors for this decrement, indicating that the changes in PS might reflect a habituation process. On this basis it is hypothesized that an increase in PS time in the mouse is a specific response to a significant environmental stimulus and could, therefore, form part of the coping strategy. This hypothesis is generalized and discussed in terms of its implications, both for experimentation concerned with measuring PS times and with the possible functional significance of PS.

Effets du jeûne sur les phénomènes phasiques du sommeil paradoxal de la souris

In C57Br/cd/Orl mice, the effects of water and/or food deprivation were considered in relation to weight, amounts of vigilance states, patterns of the peripheric phasic phenomena (eyes, whiskers and tongue movements) during paradoxical sleep. A 24 hr complete fasting provokes a loss of weight (−15%) a decrease in paradoxical sleep (−87%) and in slow wave sleep (−49%). While the frequency of the tongue movements during PS is not altered by fasting, the patterns of these movements are modified according to the experimental situation.

Effect of chronic manganese intoxication on the sleep-wake cycle in the rat

Chronic manganese intoxication elicits in the rat an increase in slow wave sleep and a decrease in paradoxical sleep by modification of the length of the phases. The similarities between this observation and the sleep disturbances observed in man in Parkinson's disease and chronic manganese poisoning are discussed.

Brain dopamine receptors and sleep in the rat: Effects of stimulation and blockade

A high dose of apomorphine, a stimulator of brain dopamine receptors, caused a reduction in total sleep, intermediate sleep and a delayed appearance of paradoxical sleep. With a lower dose, a small and not significant trend toward an increase of paradoxical sleep was observed. Spiroperidol, considered as a specific blocker of dopamine receptors, produced a dose-dependent increase of total sleep and a decrease of paradoxical sleep. Chlorpromazine induced a different effect, that is clear enhancement of paradoxical sleep. Taken together, these results indicate that an activation of dopamine systems in the brain is partly involved not only in behavioral activation, but also in corticl activation of waking and paradoxical sleep. The effect of chlorpromazine on paradoxical sleep cannot be attributed to the antidopaminergic properties of this drug.

Differences in sleep in patients with parkinson's disease

Twenty-three Parkinson patients were recorded during 2 or 3 consecutive nights. Their treatment, if any, was withdrawn for at least 15 days before the first recording session. Some qualitative abnormalities were noticed during each night in 13 of these patients. They consisted in: 1. 1. Repetitive blinking at the beginning of the night when the lights were turned off, persistence of the electromyographic activity of the chin muscles during paradoxical sleep, occurrence of rapid eye movements and blepharospasms during slow wave sleep before the onset of paradoxical sleep episodes, and alpha rhythm during paradoxical sleep. 2. 2. The study of these signs showed that association between blinking and persistence of the activity of the chin muscles during paradoxical sleep is never encountered. 3. 3. The patients with chin muscle activity during paradoxical sleep had a 50% decrease in paradoxical sleep as compared with the group of patients with repetitive blinking. 4. 4. The possibility that lesions of the locus coeruleus are responsible for this decrease in paradoxical sleep is discussed.

The effect of lesions of ascending noradrenaline pathways on sleep and waking in the rat

The role of ascending noradrenaline (NA) containing neuronal systems in sleep and waking mechanisms in the rat was investigated by making selective lesions of these systems with the neurotoxic compound 6-hydroxydopamine (6-OH-DA). The 6-OH-DA (1–16 μg) was injected intracerebrally close to the ascending NA axons in the mesencephalon. After the injection the EEG and EMG were continuously recorded for 4–8 days and the time the animal spent in waking and in different sleep states was measured. Determination of endogenous NA in the forebrain, histochemical analysis of NA varicosities in the cerebral cortex and measurement of uptake-retention of [ 3H]NA in slices from the cerebral cortex were performed 25–40 days after the injection to evaluate the lesion of the NA axons produced by 6-OH-DA. The 6-OH-DA induced lesion of catecholamine (CA) axons was reflected by acute retrograde accumulations of CA in the axons and long-term anterograde degeneration of nerve terminals as revealed by disappearance of uptake and storage of NA. Two days after surgery, a dose dependent unspecific damage of brain tissue was observed at the site of 6-OH-DA injection. The unspecific changes were much less pronounced 25–40 days after the injection than after 2 days. The degree of damage to the NA neurons, however, was largely independent of the amount given indicating a selective action of 6-OH-DA on NA axons. EEG waking as characterized by low voltage fast activity (desynchronized activity) was markedly suppressed acutely following a lesion of the ascending dorsal CA bundle. Instead the recordings exhibited a corresponding increase in periods dominated by high voltage slow waves and more synchronized activity. In spite of these changes, behavioral wakefulness seemed unaffected by the lesion. There was no difference from saline injected controls in the time spent in slow wave sleep as characterized by continuous high voltage slow waves and behavioral sleep, whereas a small decrease in paradoxical sleep was seen. The decrease in EEG waking was most pronounced during the first 4 days after the lesion. Thereafter a gradual recovery of waking activity started and recordings made 1 month later showed that the animals had regained a normal amount of EEG waking. The acute EEG changes observed were independent of the amount of 6-OH-DA injected. Injection at different sites also did not seem to influence the results. There was, however, a good correlation between the time of EEG waking and the degree of lesion of the dorsal CA bundle. The findings suggest that the NA neurons of the locus coeruleus projecting via the dorsal CA bundle to certain forebrain areas, e.g., the cerebral cortex, are important for maintenance of the electrocortical aspects of waking.

Development of sleep and wakefulness in the foetal lamb

The evolution of cortical activity was studied from 0.6 of term in utero in eleven foetal lambs, and through most of parturition and the early post-partum period in two newborn lambs. At 0.8 of term the alternating periods of wakefulness and sleep were definite. During a period of electrocorticographic desynchronization paradoxical sleep could be recognized by the return to slow wave sleep that occurs at the sounding of a bell and also by rapid eye movements. No apparent major modification of electrocortical activity accompanied the transition from intra-uterine to extra-uterine life. At parturition there was a sudden increase in muscular tone and a 50% decrease in paradoxical sleep.

Electroencephalographic study of the effects of methysergide on sleep in the rabbit

The effects of methysergide, a serotonin (5-HT) blocking agent, on the sleep-wakefulness cycle were studied in nine male rabbits with chronically implanted electrodes for the EEG, the EMG of the neck muscles and the oculogram. Methysergide (1.0 and 4.0 mg/kg) markedly delayed the occurrence of the first episode of paradoxical sleep, increased the percent time of the alert stage and decreased that of slow wave and of paradoxical sleep in the 6 h recordings made immediately after the injections. These effects of methysergide were more marked on paradoxical sleep than on slow wave sleep. Prolonged observations following single injections of 4.0 mg/kg of methysergide demonstrated not only a decrease in paradoxical sleep but also a tendency to a rebound on the 3rd day with return toward normal levels on the 4th day. With chronic administration of 1.0 mg/kg of methysergide 4 days in succession, clear decreases in both phases of sleep were observed only on the 1st day. On drug withdrawal, a marked rebound of paradoxical sleep occurred. We consider that these effects, decreases in both phases of sleep, were caused by the 5-HT blocking action of methysergide in the brain. The present results provide additional support for the hypothesis that 5-HT plays an important role in the production of sleep. However, our results also indicate that in the rabbit, the role of 5-HT is more important in paradoxical sleep than in slow wave sleep.