Ther Umsch 2000 Jul;57(7):417-20 [Why do we sleep? Contributions from animal research]. [Article in German] Tobler I Institut fur Pharmakologie und Toxikologie, Universitat Zurich. tobler@pharma.unizh.ch Despite the almost ubiquitous presence of sleep and the sleep stages nonREM and REM sleep in mammals and birds, the functions of sleep still remain elusive. Several promising approaches may shed light on this problem. Thus investigation of sleep-like states such as hibernation and torpor have shown that these states are more similar to sleep deprivation than to sleep. Furthermore, sleep-like states, which are homeostatically compensated for after rest deprivation have been found in Drosophila. These results allow to search for genes and gene products which change as a function of the vigilance states in these more simpler organisms. Thereafter, homologous genes can be investigated in mice. Publication Types:     Review   Review, tutorial PMID: 10953646, UI: 20409766 ----------

J Sleep Res 1992 Jun;1(2):125-127 Models of sleep regulation in mammals. Tobler I I, Franken P, Trachsel L, Borbely AA Institute of Pharmacology, University of Zurich, Zurich, Switzerland. [Record supplied by publisher] A brief overview of models on the regulation of sleep/waking or rest/activity is provided. Applications of the two-process model are illustrated in two species: The homeostatic facet of the model (Process S) was used to quantitatively simulate sleep in the rat and guinea pig. The model parameters were estimated for rat sleep by an optimization procedure. A close correspondence between the time course of slow-wave activity and Process S was obtained for both species under baseline conditions. Whereas in the rat a close fit was obtained also for the recovery period from sleep deprivation, some discrepancies were present in the guinea pig. It is concluded that the concept of sleep homeostasis that has been elaborated and formalized in the two-process model for human sleep, can also be applied to simulate sleep in other mammals. PMID: 10607039 ----------

J Clin Invest 1994 May;93(5):1930-9 Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. Dinges DF, Douglas SD, Zaugg L, Campbell DE, McMann JM, Whitehouse WG, Orne EC, Kapoor SC, Icaza E, Orne MT Unit for Experimental Psychiatry, Institute of Pennsylvania Hospital, Philadelphia, Pennsylvania 19139. The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep. PMID: 7910171, UI: 94237955 ----------

Sleep 1987 Aug;10(4):313-29 Temporal placement of a nap for alertness: contributions of circadian phase and prior wakefulness. Dinges DF, Orne MT, Whitehouse WG, Orne EC Unit for Experimental Psychiatry, Institute of Pennsylvania Hospital, Philadelphia 19139-2798. Napping can enhance alertness during sustained wakefulness, but the importance of the temporal placement of the nap between days and within the circadian cycle remains controversial. To resolve these issues, a between-groups study was conducted with 41 healthy, young adults permitted a 2-h nap at one of five times during a 56-h period otherwise devoid of sleep. Naps were placed 12 h apart, near the circadian peak (P) or trough (T), and were preceded by 6, 18, 30, 42, or 54 h of wakefulness. Visual reaction time (RT) performance, Stanford Sleepiness Scale (SSS) ratings, and sublingual temperature were assessed every few hours throughout the 56 h, which took place in an environment free of time cues. All groups displayed a circadian-modulated decline in RT measures and increases in SSS functions as sleep loss progressed. A nap placed at any time in the protocol improved RT performance, particularly in the lapse domain, but not SSS ratings. Comparisons within groups of circadian temperature cycles for the first versus second day of the protocol indicated that early naps (P6, T18, P30) tended to prevent the mean drop in temperature across days. The earlier naps (P6, T18) yielded more robust and longer lasting RT performance benefits, which extended beyond 24 h after the naps, despite the fact that they were comprised of lighter sleep than later naps. Circadian placement of naps (P vs. T) did not affect the results on any parameter. In terms of temporal placement, therefore, napping prior to a night of sleep loss is more important for meeting subsequent performance demands than is the circadian placement of the nap. SSS ratings suggest that the napper is not aware of these performance benefits. Because the longest lasting RT gains followed early naps, which were composed of less deep sleep than later naps, napping during prolonged sleep loss may serve to prevent sleepiness more readily than it permits recovery from it. PMID: 3659730, UI: 88017669 ----------

Dinges DF Studies of experimentally altered human sleep-wake cycles have shown that rapid eye movement (REM) sleep propensity exhibits a circadian periodicity, while slow wave sleep (SWS) is primarily responsive to the duration of prior wakefulness. What is not known is the extent to which REM sleep continues to show a circadian pattern under intense sleep pressure, and the extent to which SWS remains responsive to prior wakefulness at opposite phases of the circadian cycle. These questions were addressed by permitting healthy young adults a 2 h nap opportunity at opposite phases of the circadian cycle and with varying amounts of prior wakefulness, during a 54 h trial in a laboratory environment free of time cues. Three groups slept near the circadian peak (15.00 h) in the diurnal activity cycle, preceded by either 6, 30, or 54 h of prior wakefulness. Two other groups had naps near the circadian trough (03.00 h), midway between the peak naps and preceded by either 18 or 42 h of wakefulness. Comparisons both between and within groups revealed that latencies to sleep onset and to SWS decreased, while stage 4 sleep increased markedly in response to prior wakefulness up to 30 h, without any effect from the circadian placement of the nap. REM sleep propensity, as measured by the number of naps with REM and the amount of REM sleep among those naps that contained REM, was affected only by the circadian phase of the nap, with trough naps containing significantly less REM. Thus, no amount of sleep pressure changed the circadian phase-dependent expression of REM, and SWS remained wake-responsive at both phases of the diurnal cycle. PMID: 2427317, UI: 86300560

Behav Brain Res 1994 Aug 31;63(2):205-11 Room light impairs sleep in the albino rat. Tobler I, Franken P, Alfoldi P, Borbely AA Institute of Pharmacology, University of Zurich, Switzerland. Since the rat is a nocturnal animal sleep experiments in this species are commonly performed during the light period of the 24-h light-dark (LD) cycle. To examine whether light itself affects sleep, chronically implanted albino rats were continuously recorded for a day under a 12-h light-12-h dark cycle (light intensity approx. 300 lx) and on the subsequent day in constant darkness (DD). In the absence of light, EEG slow-wave activity (0.75-4.0 Hz) in non-REM sleep and sleep continuity were significantly enhanced, while total sleep time and cortical temperature were not affected. The results show that in the albino rat room light impairs sleep by reducing its intensity and continuity. PMID: 7999304, UI: 95092245 ----------

Encephale 1992 Jan;18 Spec No 1:45-50 The role of sleep and wakefulness in the genesis of depression and mania. Kasper S, Wehr TA Psychiatric Department, University of Bonn, FRG. Disturbances of the sleep-wake cycle are frequently seen in affective illness and are exhibited in other psychiatric illness as well. In addition to being a useful research probe, manipulations of the sleep-wake cycle such as sleep deprivation (SD) and phase advance can cause depression to remit and thus can be used as alternative or as adjunctive to pharmacologic treatment. The antidepressant response to SD occurs whether antidepressant drugs are administered or not. However, there is some evidence that the concomitant use of antidepressants may prevent the relapses that occur after recovery sleep. Data from clinical investigations also indicate that disrupted sleep can trigger and intensify mania. Rapid cycling bipolar patients may be especially vulnerable to mania/hypomania after disrupted sleep or SD. Characteristic changes in body temperature have been recorded in sleep deprivation as well as in other antidepressant treatment modalities. Thermoregulatory physiology may therefore provide a framework for understanding the effects of sleep-wake manipulations in affective illness. Publication Types:   Review   Review, tutorial PMID: 1600904, UI: 92289617 ----------

Br J Psychiatry 1991 Oct;159:576-8 Sleep-loss as a possible mediator of diverse causes of mania. Wehr TA Clinical Psychobiology Branch Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland USA 20892. When sleep duration and mood were monitored longitudinally in a 59-year-old woman with bipolar illness, sleep loss appeared to mediate the triggering of mania by psychosocial and pharmacological precipitating factors. This interpretation was supported by observations that mania could repeatedly be induced experimentally by depriving her of sleep for one night. The patient's data illustrate how sleep-loss might be a preventable cause of mania in a variety of situations. PMID: 1751874, UI: 92089738 ----------

Psychiatry Res 1990 Jun;32(3):253-63 Influence of environmental factors on suicidal behavior. Souetre E, Wehr TA, Douillet P, Darcourt G National Institute of Mental Health, Bethesda, MD 20892. The regional distribution of completed suicide was analyzed in 19 regions of France for the years 1975 and 1983. The regional distributions of environmental variables (ambient temperature, sunlight duration, and precipitation) and of sociological factors (social cohesion, socioeconomic status, status of women, and social support) were then correlated using Pearson coefficients, stepwise regression analysis, and partial correlations. Our main finding is that environmental factors such as ambient temperature may play a role in the regional distribution of completed suicide in France. Both the stepwise regression analysis and the controlled regression analysis revealed that, among all the variables studied (environmental and sociological), the main factors affecting the regional distribution of suicide were ambient temperature and sunlight duration. To our knowledge, this is the first detailed study demonstrating a clear relationship between environmental variables and suicidal behavior. The finding may be consistent with the recent description of forms of affective disorders occurring in relationship to environmental factors. PMID: 2388966, UI: 90356661 ----------