Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats: Correlation to Behavioural Activity State,Effect of Handling and Tail-Pinch

Hippocampal extracellular levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were monitored with the microdialysis technique in freely moving rats. In one experiment 30 min samples were collected during 24 h of continuous perfusion, and the monoamine output was compared to the behavioural activity state, as arbitrarily classified in three categories: sleep/rest, drowsiness and full alertness associated with complex behaviours. In the individual animal the hippocampal NA and 5-HT output showed pronounced fluctuations during the 24 h period, but the 30 min sampling times did not allow for a clear-cut correlation to behavioural activity state. However, the mean NA and 5-HT output for all animals during the dark period of the day was 43 and 38% higher, respectively, than during the light period, and the average NA and 5-HT levels in samples collected during periods of high behavioural activity was 34 and 45% higher, respectively, than during periods of rest or sleep. In contrast, there were no detectable changes in extracellular 5-HIAA. The selective serotonin uptake blocker indalpine, added to the perfusion fluid at 1 microM, increased the extracellular 5-HT levels 6-fold, with a similar correlation to behavioural activity state as without indalpine. In a second experiment the effect of handling and tail-pinch was studied in 15 min sample fractions. Gentle handling of the animals during the sampling period increased the hippocampal NA and 5-HT output by 32 and 72%, respectively, and a similar increase (63 and 48%) was obtained by application of tail-pinch. Maximum NA output was reached during the handling or tail-pinch period, whereas maximal 5-HT levels were detected in the subsequent 15 min sample fraction. No changes in extracellular 5-HIAA was observed. It is concluded (1) that intracerebral microdialysis provides a useful method for the study of extracellular NA and 5-HT in the hippocampal formation of conscious rats during active behaviour; (2) that there are substantial fluctuations in hippocampal NA and 5-HT output in freely moving rats which correlate with the light - dark cycle as well as with the activity state of the animals; (3) that the spontaneous variations in 5-HT output are maintained during reuptake blockade; and (4) that behavioural activation through gentle handling or tail-pinch elicits NA and 5-HT release. The present data support a role of the forebrain NA and 5-HT systems in behavioural state control and highlights the necessity of experimental designs in which the spontaneous fluctuations in transmitter release are controlled for in studies of, for example, drug effects on NA and 5-HT release in conscious animals.     

Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor

Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.     

How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms.     

Inhibition of tumor necrosis factor in the brain suppresses rabbit sleep

Tumor necrosis factor (TNF) is a cytokine that possesses many biological activities, including enhancement of non-rapid-eye-movement sleep (NREMS). The role of endogenous TNF in the regulation of spontaneous sleep is unknown. If TNF is involved in sleep regulation, then reduction of endogenous TNF should suppress spontaneous sleep. A soluble TNF-binding protein I (TNF-BP I) and a synthetic fragment of TNF-BP I, TNF-R-(159–178), that contains the biologically active region of TNF-BP I, were used. These substances bind TNF and possess TNF-inhibitory activity; their effects on rabbit sleep after intracerebroventricular injection were determined across a 6-h recording period. Two doses of TNF-BP I (0.05 g and 0.5 g) were administered; the higher dose of TNF-BP I significantly decreased NREMS. Four doses of TNF-R-(159–178) (0.25 g, 2.5 g, 25 g and 50 g) were used. The 25 g and 50 g doses significantly suppressed NREMS. The highest dose (50 g) also decreased REM sleep. These results are consistent with the hypothesis that endogenous brain TNF is involved in the regulation of normal sleep.     

A sleep disturbance in high risk for SIDS infants

A developmentally immature sleep pattern has been identified in infants with a recent history of an unexplained life-threatening episode of sleep apnoea who are considered at risk for SIDS. In these infants there is a persistence of Sleep Onset REM Periods (SOREMPS) after prolonged wakefulness when compared to controls matched for age, sex, birthweight and race. This sleep characteristic has not been previously reported.     

Hypertension and sleep apnoea

SUMMARY  Epidemiological data indicate a link between sleep-disordered breathing and elevation of arterial pressure. Previous studies suggest increased activity of the sympathetic nervous system in patients with sleep apnoea. The response of muscle sympathetic nerve activity was further investigated in normal, awake subjects following exposure to 20 minutes of asphyxia. Sympathetic nerve traffic increased during exposure and remained elevated even after the return to room air breathing. These findings raise the possibility that this sustained elevation of sympathetic nerve traffic could play a role in the development of daytime hypertension in patients with sleep-disordered breathing.     

Sleep in seasonal affective disorder patients in forced desynchrony: an explorative study

The majority of winter-type seasonal affective disorder (SAD) patients complain of hypersomnia and daytime drowsiness. As human sleep is regulated by the interaction of circadian, ultradian and homeostatic processes, sleep disturbances may be caused by either one of these factors. The present study focuses on homeostatic and ultradian aspects of sleep regulation in SAD. Sleep was recorded polysomnographically in seven SAD patients and matched controls subjected to a 120-h forced desynchrony protocol. In time isolation, subjects were exposed to six 20-h days, each comprising a 6.5-h period for sleep. Patients participated while being depressed, while remitted after light therapy and in summer. Controls were studied in winter and in summer. In each condition, the data of each subject were averaged across all recordings. Thus, the influence of the effects of the circadian pacemaker on sleep was excluded mathematically. The comparison of patients with controls and with themselves in the various conditions revealed no abnormalities in homeostatic parameters: sleep stage variables, relative power spectra and time courses of power in various frequency bands across the first three non-rapid eye movement-rapid eye movement (NREM-REM) cycles showed no differences. The data suggest that homeostatic processes are not involved in the disturbance of sleep in SAD.     

Genetic epidemiology of cystic fibrosis in Saguenay-Lac-St-Jean (Quebec, Canada)

Cystic fibrosis (CF) is an autosomal recessive disorder with a prevalence at birth estimated at 1/2000-1/2500 livebirths in Caucasian populations. Some 127 CF individuals are known in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of Quebec. The prevalence at birth was estimated at 1/902 live borns, and the carrier rate was estimated at 1/15 inhabitants in the SLSJ region. The mean inbreeding coefficient was only slightly elevated in the CF group compared with three control groups, and was due to remote consanguinity. The mean kinship coefficient was 2.4 times higher in the CF group than in the control groups. In SLSJ region, the places of origin of the CF individuals and their parents did not show a clustered nonuniform distribution. Endogamy was not higher in the CF group than in control groups.     

The meaning of good sleep: a longitudinal study of polysomnography and subjective sleep quality

SUMMARY  The present study sought to investigate the meaning of subjectively good sleep, using a longitudinal and intraindividual design. Eight subjects slept in an isolation unit according to an irregular schedule of 6h sleeps and 1h naps, designed to give normal amounts of time in bed (1/3 of total), but variable sleep quality. Eight sleeps and eight naps were used for longitudinal simple and multiple regression analyses with standard polysomnographical sleep variables as predictors and subjective sleep quality as dependent variables. The results showed that subjective sleep quality (and related variables) was closely related to sleep efficiency, but not sleep stages. At least 87% efficiency was required for ratings of 'rather good' sleep. In addition, sleep quality ratings improved with closeness (of the awakening) to the circadian acrophase (17.00–21.00 hours) of the rectal temperature rhythm. The subjective ease of awakening differed from most other other variables in that it was related to low sleep efficiency. Objective and subjective homologues of sleep length and sleep latency showed high mean intraindividual correlations ( r = 0.55 and 0.64, respectively). It was concluded that objective measures of sleep continuity were closely reflected in perceived sleep quality and that sleep quality essentially means sleep continuity.     

Pre-screening via sleep logs in sleep-disordered patients—Adaptational effects, yes or no?

Summary Question of the study  Sleep logs are common tools in sleep research and clinical routine. Usually sleep logs have to be completed during a 2-week period, with the first week serving as an adaptation to the instrument itself. In the present study, we investigated whether there is indeed such an adaptation bias or not. Patients and methods  A total of 236 chronically sleep-disordered outpatients completed the standardized sleep log ‘Abend-Morgen-Protokoll’ during a 2-week pre-screening period prior to the first visit in our sleep ambulance. Two sets of items were established, the ‘instrumental’ and the ‘therapeutic’ set. The respective ratings of the first and second week (week A, B) were compared to evaluate clinically relevant changes. Results  The ratings of several ‘instrumental’ items significantly differed between week A and B. However, these changes—on average—were only marginal and therefore of little clinical importance. Regarding the ‘therapeutic’ set of items, no systematic variations could be ascertained over the assessment period. Conclusion  The present investigation could not confirm the presence of adaptation biases (instrumental, therapeutic) in a large sample of chronically sleep-disordered outpatients. Therefore, we consider a 1-week pre-screening period via sleep log as sufficient for the diagnostic process in these patients.