Biomedical subjects

M Lancel

Publications and source records attributed to M Lancel.

33 records · Page 2Linked to original sources

PubMed1996

The GABAA agonist THIP (gaboxadol) increases non-REM sleep and enhances delta activity in the rat.

To investigate the effects of the selective gamma-aminobutyric acid (GABA)A receptor agonist 4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol (THIP) on sleep, vehicle or 2 or 4 mg kg-1 of THIP were randomly administered i.p. to 8 rats at light onset. EEG and EMG were recorded during the first 6 hours after injection. THIP 4 mg kg-1 transiently evoked bursts of absence epilepsy-like EEG hypersynchronization. It significantly promoted non-rapid eye movement (non-REM) sleep and elevated delta activity within non-REM sleep. This was accompanied by an increase in both the rise rate and maximal level of delta activity within the non-REM sleep episodes. The effects of THIP on sleep resemble those reported earlier for the GABAA agonist muscimol and are dissimilar from those induced by benzodiazepine-agonistic modulators of GABAA receptors. These data indicate that agonists and agonistic modulators of GABAA receptors affect sleep differentially.

Animals↗

PubMed1996

Role of GABAA receptors in sleep regulation. Differential effects of muscimol and midazolam on sleep in rats.

To assess the influence of the gamma-aminobutyric acid (GABA)A receptor on sleep and sleep EEG, rats were injected intraperitoneally with vehicle, two doses of muscimol (0.2 and 0.4 mg/kg), a selective GABAA agonist, and midazolam (3 mg/kg), a benzodiazepine-GABAA agonist. EEG and EMG recordings were made for 6 or 8 hours. Muscimol dose-dependently increased the amount of nonrapid eye movement sleep (nonREMS) and REMS. The higher dose of muscimol enhanced EEG activity over almost the entire frequency range (0.5-25 Hz), including delta (0.5-4 Hz) and sigma (11-16 Hz) activity, within nonREMS and in the frequencies over 10 Hz within REMS. Midazolam also increased the amount of nonREMS. However, most of the other effects of midazolam contrasted the effects of muscimol: midazolam decreased REMS, reduced low frequency (< or = 11 Hz) EEG activity within nonREMS, and enhanced the activity in higher frequencies during both nonREMS and REMS. These data demonstrate the involvement of GABAA receptors in the regulation of sleep-wake behavior as well as in the generation of spindles and delta waves during nonREMS. The effects of these two GABAA agonists indicate that activation of different binding sites on the GABAA receptor complex differentially affect sleep states and sleep EEG.

Animals↗

PubMed1996

Progesterone induces changes in sleep comparable to those of agonistic GABAA receptor modulators.

There is much evidence that progesterone has hypnotic anesthetic properties. In this vehicle-controlled study, we examined the effects of three doses of progesterone (30, 90, and 180 mg/kg) administered intraperitoneally at light onset on sleep in rats. Progesterone dose dependently shortened non-rapid eye movement sleep (NREMS) latency, lengthened rapid eye movement sleep (REMS) latency, decreased the amount of wakefulness and REMS, and markedly increased pre-REMS, an intermediate state between NREMS and REMS. Progesterone also elicited dose-related changes in sleep state-specific electroencephalogram (EEG) power densities. Within NREMS, EEG activity was reduced in the lower frequencies (< or = 7 Hz) and was enhanced in the higher frequencies. Within REMS, EEG activity was markedly enhanced in the higher frequencies. The effects were maximal during the first postinjection hours. The concentrations of progesterone and the progesterone metabolites 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one, both positive allosteric modulators of gamma-aminobutyric acid A (GABAA) receptors, were determined at different time intervals after vehicle and 30 or 90 mg/kg progesterone. Progesterone administration resulted in dose-dependent initially supraphysiological elevations of progesterone and its metabolites in the plasma and brain, which were most prominent during the first hour postinjection. The effects of progesterone on sleep closely resemble those of agonistic modulators of GABAA receptors such as benzodiazepines and correlate well with the increases in the levels of its GABAA agonistic metabolites. These observations suggest that the hypnotic effects of progesterone are mediated by the facilitating action of its neuroactive metabolites on GABAA receptor functioning.

Animals↗

PubMed1996

Effect of interleukin-1 beta on EEG power density during sleep depends on circadian phase.

The cytokine interleukin (IL)-1 is a key mediator of the somnogenic response to immune challenge. In this vehicle-controlled study we evaluated circadian interference with the sleep-promoting effects of IL-1 beta. In two randomized experiments, rats were injected intracerebroventricularly with 5 ng IL-1 beta either at the beginning of the rest phase or at the beginning of the activity phase. Recordings were made during the 24 h preceding the injections (baseline) and during the first 12 postinjection hours. To avoid masking effects of light, the rats were maintained under a skeleton photoperiod during recording. During both the rest and activity phase, IL-1 beta induced fever and initially promoted non-rapid eye movement sleep (REMS). The effect of IL-1 beta on the duration of non-REMS and electroencephalogram (EEG) power densities within non-REMS was related to circadian phase. During the rest phase, IL-1 beta resulted in a minor increase in non-REMS duration but a prominent enhancement in EEG activity in the delta (0.5-4 Hz) and most other frequency bands. During the activity phase, IL-1 beta evoked a larger increase in the duration of non-REMS but hardly affected EEG activity within this state. Thus the effects of IL-1 beta on non-REMS are strongly influenced by diurnal phase. The alterations in EEG power density are in contrast to those elicited by sleep deprivation, which are largely independent of time of day. It is concluded that IL-1 beta activates EEG regulatory mechanisms mediated by processes that depend on circadian phase.

Animals↗

PubMed1995

Lipopolysaccharide increases EEG delta activity within non-REM sleep and disrupts sleep continuity in rats.

Activation of the immune system by microorganisms or specific microbial constituents promotes non-rapid-eye-movement (REM) sleep (non-REMS). In this study, we assessed the effects of lipopolysaccharide (LPS) on sleep duration, electroencephalogram (EEG) power spectra, and brain temperature (Tbr) in rats. Twenty-four hour recordings were made before and after intraperitoneal injection of vehicle or 30 or 100 micrograms/kg LPS at lights on. During the first 12 h after administration of both doses of LPS, Tbr was elevated, REMS duration was reduced, and non-REMS duration was unchanged, whereas the non-REMS episodes were shortened. EEG activity within non-REMS from 0.5 to 7 Hz was enhanced during hours 3-12. During the second 12-h period, the number of non-REMS and REMS episodes and the total time in both states were increased. EEG activity within non-REMS was mainly reduced in the entire frequency range (0.5-25.5 Hz). The effects of LPS did not differ between the doses. The effects of LPS on EEG power spectra are similar to those observed after sleep deprivation, i.e., a physiological intensification of non-REMS, indicating that both manipulations may activate common sleep EEG regulatory mechanisms. However, the disruption of non-REMS continuity following LPS administration at light onset contrasts the changes induced by sleep deprivation and may reflect an effect of a systemic inflammatory response on sleep maintenance.

Animals↗

PubMed1994

Pregnenolone enhances EEG delta activity during non-rapid eye movement sleep in the rat, in contrast to midazolam.

Several endogenous steroids exert their neuroactivity through non-genomic effects and act as potent GABAA receptor-agonists or-antagonists. To examine the influence of the main precursor of these steroids on sleep-wake behaviour, pregnenolone (400 micrograms) was dissolved in oil and administrated s.c. to 8 rats at the beginning of the light period. For comparison, the benzodiazepine midazolam was also injected (3 mg/kg). The effects on the amounts of the vigilance states and on the EEG signals within each state were investigated during 24 hours. Compared to control vehicle, pregnenolone did not significantly affect the duration of the vigilance states. However, delta activity (0.5-4 Hz) within non-rapid eye movement sleep (nonREMS) was enhanced throughout the recording period. Midazolam increased nonREMS, decreased wakefulness and, transiently, also suppressed rapid eye movement sleep (REMS). Spectral analysis of the EEG within nonREMS showed a long lasting reduction in delta and theta activity (4-9 Hz) and a shorter lasting enhancement in the higher frequencies (10-25 Hz). EEG activity within REMS and wakefulness was elevated in the higher frequencies (> or = 10 Hz) during the the first half of the recording period. We conclude that in the rat, the effects of midazolam on EEG activity closely resemble those of benzodiazepines in other mammalian species. The influence of pregnenolone on EEG delta activity within nonREMS indicates that pregnenolone acts as an inverse GABAA-benzodiazepine agonist.

Animals↗

PubMed1993

Cortical and subcortical EEG in relation to sleep-wake behavior in mammalian species.

In humans and several other mammals, a quantitative EEG analysis has been used to study the regulation of sleep-wake behavior. In all mammalian species studied, cortical EEG recorded during non-REM sleep (NREMS) is characterized by the occurrence of spindles and high voltage, slow waves (0.5-4.0 Hz). Furthermore, slow-wave activity (SWA) is low at the beginning of a NREM episode and it rises in the course of a NREM episode. The rise rate and the maximal level of SWA are a monotonic function of the duration of prior wakefulness. During REMS, cortical EEG typically exists of low-voltage, mixed frequencies and, in some animals, a prominent theta rhythm is superimposed. Only after sleep deprivation in some species does cortical EEG within REMS change. Especially, the EEG activity during wakefulness depends considerably on the behavioral state, on the electrode location and on the species. On average, cortical EEG within wakefulness consists of low-voltage, mixed frequencies. The few studies done on subcortical EEG clearly show that the electrical activity differs highly between brain regions and between species. However, two recent studies, in which a spectral analysis of subcortical EEG was made, showed that, at least in humans and cats, the changes occurring in subcortical EEG associated with changes in sleep-wake behavior parallel the general characteristics of cortical EEG described above.

Animals↗

PubMed1992

The time course of sigma activity and slow-wave activity during NREMS in cortical and thalamic EEG of the cat during baseline and after 12 hours of wakefulness.

The extrapolation from recent neurophysiological findings concerning the dependency of spindle and slow-wave oscillations of thalamocortical neurons on membrane potential to macroscopic EEG events, predicts a reciprocal relation between spindle activity and slow-wave activity (SWA) in thalamic and cortical EEG during non-rapid-eye-movement sleep (NREMS). To test this hypothesis, the EEG recorded in 8 cats, from the nucleus centralis lateralis of the thalamus and from the skull during a 12-h baseline dark period and during a 12-h recovery dark period, following a 12-h sleep deprivation, were analyzed. Per 12-s epoch, sleep-wake behaviour was determined and spectral power density was computed in the slow-wave frequency range (0.5-4.0 Hz) and in the spindle frequency region (sigma activity: 11.0-14.5 Hz). To analyze the development of EEG power densities in the course of NREMS and during the transition from NREMS to REMS, the last epoch of wakefulness and the first 15 epochs of NREMS, as well as the last epochs of NREMS and the first epoch of REMS were selected from the NREM-REM cycles. For each animal the values were averaged over 4-h intervals. In the cortical EEG, SWA was minimal at NREMS onset and increased progressively in the course of NREMS. SWA declined sharply prior to REMS. sigma Activity increased gradually towards a uniform level after NREMS onset. During the transition to REMS, sigma activity initially increased and then decreased rapidly. In the thalamic EEG, the time course of SWA paralleled that of the cortex. However, the development of sigma activity during the first part of NREMS differed: in the thalamic EEG, sigma activity was maximal during the beginning of NREMS and slightly decreased thereafter. After sleep deprivation, SWA within NREMS was markedly enhanced in both the cortical and the thalamic EEG. Sigma activity was attenuated in the thalamic EEG, whereas in the cortical EEG it was temporarily elevated. The present data show that, in the thalamic EEG, an inverse relation exists between spindle and slow-wave activity during baseline NREMS. This relation is preserved after sleep deprivation. In the cortical EEG, a reciprocal relation between spindling and SWA is less evident.

Animals↗

PubMed1992

Enhanced slow-wave activity within NREM sleep in the cortical and subcortical EEG of the cat after sleep deprivation.

Electroencephalograms (EEGs) of the cortex and of seven subcortical structures were recorded during two baseline days and during a recovery day following a 12-hour period of sleep deprivation (SD) in eight cats. The EEGs were analyzed by visual scoring and by spectral analysis. The following subcortical structures were studied: hippocampus, amygdala, hypothalamus, nucleus centralis lateralis of the thalamus, septum, nucleus caudatus and substantia nigra. The EEGs of all brain structures exhibited sleep state-dependent changes. In general, slow-wave activity (SWA, 0.5-4.0 Hz) during nonrapid eye movement (NREM) sleep exceeded that of REM sleep. The power spectra (0.5-24.5 Hz) in NREM, as well as the relationship between the power spectra of NREM and REM sleep, differed between the recording sites. Moreover, the rate of increase of SWA in the course of an NREM episode and the rate of decrease of SWA at the transition from NREM to REM sleep differed between the brain structures. During the first 12 hours following SD, the duration of NREM increased due to a prolongation of the NREM episodes. REM increased by a rise in the number of REM episodes. During the same period, the NREM EEG power density in the delta and theta frequencies was enhanced in all brain structures. Furthermore, in all structures the enhancement of SWA was most pronounced at the beginning of the recovery period and gradually declined thereafter. SD also induced a rise in the rate of increase of SWA in the NREM episodes in all recording sites. This indicates that the enhancement of EEG power density was not only due to prolongation of the NREM episodes. The EEG activity during REM was barely affected by the SD. It is concluded that, in all brain structures studied, the EEG during NREM is characterized by high levels of SWA. Furthermore, in each brain structure, SWA within NREM sleep is enhanced after a prolonged vigil. These data may indicate that SWA reflects a recovery process in cortical and subcortical structures.

Animals↗

PubMed1991

Effects of circadian phase and duration of sleep deprivation on sleep and EEG power spectra in the cat.

The electroencephalogram (EEG) of cats was recorded under baseline conditions (LD 12:12) and after 4 and 8 h of sleep deprivation (SD). The EEG was analyzed by visual scoring and by spectral analysis. Under baseline conditions the 24-h distribution of sleep was bimodal: the smallest amounts of sleep occurred at the light-dark and dark-light transitions. EEG slow-wave activity (power density in the delta frequency range: 0.5-4.0 Hz) in non-rapid-eye-movement sleep (NREMS) showed a small variation over the 24-h period. When recovery sleep, following 4 h and 8 h of SD, started at the beginning of the dark period, no significant rebound of NREMS and REMS occurred during the 24-h recovery period. When recovery sleep, after 4 h of SD, started at the fifth hour of the light period, the amount of NREMS was increased. In all experiments the EEG power density in NREMS was enhanced after SD in the entire frequency range studied (0.5-31.5 Hz), but more prominently in the delta and theta (4.5-7.0 Hz) frequency bands. The effects dissipated in the course of the recovery period. The magnitude and duration of the enhancements of EEG power densities were dependent on the duration of SD and on the circadian phase at which SD was scheduled. It is concluded that in the cat sleep is a function of both circadian and homeostatic processes and that especially the EEG power density in NREMS is highly responsive to sleep loss.

Analysis of Variance↗

PubMed1991

Sleep structure and EEG power density in morning types and evening types during a simulated day and night shift.

The objective of this study was to examine circadian and homeostatic regulation of sleep in humans. In 8 morning types (M-types) and in 8 evening types (E-types), sleep was recorded during 3 successive nights and, after shifting sleep to the daytime, during 3 consecutive days. Night sleep was highly similar in the M-types and E-types. Day sleep clearly differed from night sleep in both types: Day sleep was shorter and had a longer first REMS episode. Furthermore, EEG power density recorded during non-REMS in the delta and theta frequency bands was higher during all day-sleep periods. Remarkably, the enhancements did not occur in non-REMS episode 1 but were delayed. This was interpreted as an inhibition of EEG power density at the beginning of sleep, possibly caused by the time course of body temperature and/or by the higher REMS propensity. Also, clear differences between the types became apparent: Only in the E-types, the non-REMS episodes shortened in response to the shift in bedtime, and probably related to this, the time course of EEG power density over consecutive non-REMS episodes became almost flat. It was concluded that the circadian system exerts not only an influence on sleep duration and REMS propensity, but also affects the time course of the non-REMS process.

Adolescent↗

PubMed1991

EEG slow wave activity, REM sleep, and rectal temperature during night and day sleep in morning-type and evening-type subjects.

During 3 baseline nights (2 for adaptation) and during 3 days of a sleep-wake reversal, electrophysiological characteristics of sleep and rectal temperature were recorded in 8 morning-type (M-type) and 8 evening-type (E-type) subjects, living in a quiet sleep laboratory. Outcomes of visual sleep scoring revealed the following general tendencies for day-sleep as compared to night-sleep: shorter sleep latencies, shorter REM (rapid eye movement sleep) latencies, advance of the time of maximum REM duration, increased duration of slow wave sleep, more intermittent wakefulness, and decreased subjective sleep quality. Furthermore, for the M-types consistently shorter sleep latencies and--for day-sleep--longer REM latencies were observed than those for the E-types. With regard to the parabolic time course of REM duration, M-types appeared to be relatively phase advanced, in particular for their day-sleep. In addition, subjective sleep quality was consistently higher for the M-types, with the exception of the first day-sleep. The temporal distributions of EEG delta (0.5-3.5 Hz) energy over the first four NREM/REM cycles of day-sleep all deviated from a monotonically decreasing trend. Compared to night-sleep the M-types showed a relative increase of delta energy for Cycle 2, whereas for the E-types a relative increase for Cycles 3 and 4 was observed. An analysis of delta energy, employing a pattern-recognition technique independently from visual sleep scoring, revealed an overall faster rate of accumulation for the M-types. Following sleep onset, rectal temperature showed a decrement, which was larger for the M-types. Moreover, rectal temperature and delta energy were negatively related, as indicated by a negative mean intra-individual correlation. These results are discussed in relation to the characteristic sleep-wake behavior of M-types and E-types.

Adolescent↗

PubMed1989

Effects of repeated sleep deprivation in the dark- or light-period on sleep in rats.

This study was designed to examine the differences between sleep duration and EEG when sleep was restricted to the rest- or activity-phase for 5 successive days, achieved by repeated sleep deprivation in the dark (DSD) or light-period (LSD). In the DSD-experiment the percentages of the vigilance states were comparable to the level of the baseline light period. In LSD, the amounts of all sleep states increased substantially relative to baseline dark. The sleep episodes were lengthened in DSD and LSD. The duration of NREM-sleep and the sleep episodes remained longer in the light than in the dark, indicating circadian influences. In the first hours after sleep deprivation the delta activity during NREM-sleep was enhanced in LSD and to a lesser extent in DSD. This effect diminished over the consecutive days in both experiments. The EEG energy gained during sleep and its accumulation pattern on each day in DSD and LSD were strikingly similar, thereby reflecting a homeostatic process. After the sleep deprivation days, small changes were observed in the distribution of the vigilance states, the delta activity and EEG energy over the light- and dark-period.

Animals↗

PubMedDate not supplied

High doses of systemic DHEA-sulfate do not affect sleep structure and elicit moderate changes in non-REM sleep EEG in rats.

The hormone dehydroepiandrosterone (DHEA) and its metabolite DHEA-sulfate (DHEAS) occur in huge quantities in the plasma as well as in the brain of vertebrates. To investigate whether DHEAS modulates sleep-wake behavior, we assessed the sleep response to three doses (25, 50, and 100 mg/kg) of intraperitoneally administered DHEAS, mixed with oil, in 8 rats. DHEAS injections produced dose-dependent and long-lasting elevations in the plasma levels of both DHEAS and DHEA. DHEAS administration did not affect sleep time and architecture but exerted persistent effects on the electroencephalogram (EEG) within non-rapid eye movement sleep: 50 mg/kg DHEAS significantly augmented EEG power in the frequency range of sleep spindles, and 100 mg/kg DHEAS depressed EEG power in the slow-wave frequency bands. The findings indicate that DHEAS changes the sleep EEG in a dose-dependent way, possibly through a modulation of GABA- and glutamate-induced currents.

Analysis of Variance↗

PubMedDate not supplied

The GABA uptake inhibitor tiagabine promotes slow wave sleep in normal elderly subjects.

Aging is associated with a dramatic decrease in slow wave sleep (SWS) and sleep consolidation. Previous studies revealed that various GABA(A) agonists and the GABA uptake inhibitor tiagabine augment slow frequency components in the EEG within non-REM sleep, and thus promote deep sleep in young individuals and/or rats. In the present double-blind, placebo-controlled study, we assessed the effect of a single oral dose of 5 mg tiagabine on nocturnal sleep in ten healthy elderly volunteers (6 females). During the placebo night the subjects displayed a low sleep efficiency, due to high amounts of intermittent wakefulness, and little SWS. Tiagabine significantly increased sleep efficiency, tendentially decreased wakefulness and prominently increased both SWS and low-frequency activity in the EEG within non-REM sleep. The present findings demonstrate that tiagabine increases sleep quality in aged subjects. Moreover, the effects of tiagabine closely match those evoked by the GABA(A) agonist gaboxadol in young subjects and indicate that such compounds may have prospects in the treatment of sleep disturbances, particularly of those commonly occurring in the elderly.

Administration, Oral↗