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Sleep deprivation in the rat: II. Methodology.

Methods common to several studies in this series are described. A key feature is a sleep deprivation apparatus in which an experimental and a yoked control rat are housed on opposite sides of a divided disk suspended over shallow water. When the experimental rat enters a "forbidden" sleep stage, the disk is automatically rotated, forcing the experimental rat to walk to avoid being carried into the water. The control rat receives the same physical stimulation but can sleep ad lib when the disk is stationary.

Animals↗

Relations between depressed mood and vocal parameters before, during and after sleep deprivation: a circadian rhythm study.

The mechanism underlying improvement after total sleep deprivation (TSD) was studied in 14 major depressed patients. The suggestions that (1) circadian processes and/or (2) dimensions of arousal may play a role in the response to TSD were investigated. Diurnal variation of depressed mood and of mood- and arousal-related vocal parameters was studied in relation to the effect of TSD on depressed mood and vocal parameters. During 3 baseline days, during TSD and 2 days after TSD vocal parameters and depressed mood were assessed 6 and 3 times daily respectively. The mean fundamental frequency (frequency of vocal fold vibration, F0) (presumably reflecting aspects of arousal) as well as the range of the F0 (proposed to reflect sadness) showed a clear circadian pattern with a peak at about 4.00 p.m. TSD affected the circadian organization of the mean F0 and advanced the peak of the curve. After one night of subsequent sleep this effect disappeared. In addition, improvement after TSD coincided with an increase of the mean F0. The diurnal variation of mood before TSD predicted the mood response to TSD, whereas diurnal variation of vocal parameters did not. Moreover, circadian changes in vocal parameters were not related to changes in depressed mood. These findings suggest that the diurnal variations in mood and vocal parameters are regulated by different mechanisms. Data support the presumption that circadian as well as arousal processes are involved in the mood response to TSD. Circadian changes in vocal parameters due to TSD are not likely to reflect changes in the biological clock.

Adult↗

Differential effect of prior paradoxical sleep deprivation on conditioned taste aversion, neophobia and attenuation of neophobia to solid food in rats.

The effect of paradoxical sleep deprivation (PSD) on subsequent acquisition of conditioned taste aversion (CTA) to liquid diets is confounded by the uncertain level of thirst when using the water tank procedure. This difficulty is eliminated when examining CTA and attenuation of neophobia (AN) to solid diets. Adult male rats (n = 100) were habituated to receive their daily ration of food during a 30-min stay in a box equipped with a row of 10 feeders baited with 2-3 g pieces of moist standard diet. 24-h PSD increased neophobic rejection of novel sweet food (with added 5% saccharose), but did not influence intensity of CTA elicited by LiCl poisoning. Addition of a bitter tasting red food dye to the sweet food caused marked neophobia which was enhanced by preceding PSD. Association of this unpalatable food with LiCl elicited strong CTA which extinguished faster in the PSD-pretreated animals. On the other hand, preacquisition PSD did not influence AN to the same stimulus. Sweet food with added blue dye elicited only mild neophobia which was enhanced by preceding 24-h PSD. Preacquisition PSD did not influence AN but significantly increased CTA to blue sweet food. It is concluded that PSD can either enhance or weaken CTA and that this complex effect on food selection learning cannot be explained by PSD-induced reduction of fear.

Animals↗

The effects of paradoxical sleep deprivation and valine on spatial learning and brain 5-HT metabolism.

We have previously reported that rapid eye movement sleep deprivation (REMSD), induced by the flower pot technique, causes a deficit in reference spatial memory and increases rates of serotonin (5-HT) metabolism in the brain. In this study we used increased concentrations of dietary valine to inhibit tryptophan (TRP) transport across the blood-brain barrier in an attempt to modify the REMSD-induced increase of 5-HT metabolism. Rats were fed either a control diet or the same diet supplemented to 2% by weight valine, and were allocated to one of three experimental groups: cage control (CC), stress tank control (TC), or REMSD. Reference and working spatial memory of all rats was tested in a Morris water maze on Days 2, 3, and 4. REMSD produced a significant decrement in reference memory on Days 2 and 4, independent of dietary condition. The valine diet had a detrimental effect on the reference memory of TC rats on Day 2 but not Day 4. Measurements made on Day 4 indicated that the valine diet decreased brain TRP only in the CC rats. In contrast, the valine diet did not prevent increases in brain TRP or 5-HT metabolism in REMSD rats, and increased hypothalamic and brain stem TRP concentrations and the hippocampal 5-HIAA/5-HT ratio in TC rats. These results indicate that dietary valine does not prevent REMSD-induced changes in spatial memory or serotonin metabolism, although it does reduce brain TRP in nonstressed rats.

Animals↗

Effects of paradoxical sleep deprivation in the rabbit.

The effects of nonpharmacologically-induced deprivation of paradoxical sleep for a 24 hour period were studied in rabbits. Response characteristics commonly associated with the deprivation procedure in other species were observed, as well as features apparently peculiar to the rabbit. Like other mammals, rabbits: (1) show increased attempts to experience PS during the deprivation procedure relative to the baseline occurrence of PS; (2) become increasingly difficult to arouse from PS as the deprivation period progresses; (3) show increased amounts of PS (rebound) in post-deprivation recordings relative to baseline; and (4) compensate for only one-third of the PS deficit incurred during deprivation. Rabbits' response to PS deprivation differs from other mammals in the following ways: (1) the deprivation procedure is truly selective, significantly affecting only amounts of PS and not total sleep time or other sleep stages; (2) the rebound response is restricted to the light phase of the light-dark cycle on the first recovery day; and (3) as indexed by eye movement density, phasic activity during PS is not enhanced during the recovery period. Given that the crucial factor in the PS deprivation-compensation phenomenon is thought to be the deprivation and subsequent enhanced occurrence of phasic events, and considering that events within the oculomotor system have been emphasized in this regard, the results of this investigation suggest the existence of species differences regarding the nature and form of the compensatory response to PS deprivation.

Animals↗

Ongoing lithium treatment prevents relapse after total sleep deprivation.

Forty bipolar depressed inpatients underwent three consecutive cycles of total sleep deprivation (TSD). At the beginning of the study, 20 patients were free of psychotropic drugs and 20 had been receiving lithium medication for at least 6 months. Mood was rated on the Hamilton Rating Scale for Depression before and after TSD; perceived mood changes during treatment were evaluated with self-administered visual analog scales. Patients undergoing long-term lithium treatment showed a significantly better response to TSD as rated on both scales: 13 of 20 patients (vs. 2 of 20 patients without lithium) showed a sustained response during a follow-up period of 3 months. This preliminary evidence of a positive interaction of TSD and long-term lithium treatment could be explained by a synergistic effect of both treatments on brain serotonergic function, possibly via a desensitization of 5-hydroxytryptamine-1A inhibitory autoreceptors.

Bipolar Disorder↗

Dexamethasone suppression test combined with total sleep deprivation in depressed patients.

The effect of one night's total sleep deprivation (SD) on the dexamethasone suppression test (DST) was studied in groups of endogenously and nonendogenously depressed patients who were diagnosed according to different research classification systems. The DST was normal (less than 5 micrograms/dl) before and after SD in the group of nonendogenously depressed patients. Deterioration, no change or only slight clinical response in single items occurred. In the group of endogenous depressives 8 out of 11 were baseline nonsuppressors (greater than 5 micrograms/dl). After SD a large variability of cortisol nonsuppression was found in this group. Clinical response occurred in the majority of these patients but was more favorable in those who had a trend for normalization of DST. Clinical diagnosis as well as DST seem to have a therapy-predictive value for one night's total SD in patients with affective disorders.

Adult↗

Evaluating the influence of sleep deprivation upon circadian rhythms of exercise metabolism.

Cardiorespiratory and gas exchange responses to a moderate, standardized treadmill walking task showed a weak circadian rhythm, with larger superimposed peaks attributable to feeding. However, both rhythms became progressively attenuated during a period of sleep deprivation. A method of exploring this phenomenon is illustrated by an analysis of data on walking heart rate, respiratory minute volume, oxygen intake, and rating of perceived exertion, collected on 11 young men at 3-hr intervals during 60 hours of sleep deprivation.

Adult↗

Effect of continuous heat exposure on sleep during partial sleep deprivation.

This study examined the effects of continuous heat exposure on sleep structure during a partial sleep-deprivation regime. The experimental protocol was divided into three periods. After a baseline period (5 days and nights at 20 degrees C), the sleep of the subjects was restricted to the second half of the night (3 a.m.-7 a.m.) for four consecutive nights. The restricted-sleep period was followed by two recovery days and nights. During the deprivation and recovery periods, the ambient temperature was 20 degrees C for six of the 12 subjects and 35 degrees C for the others. Sleep, esophageal and mean skin temperatures were continuously recorded. At 20 degrees C, the expected effect of sleep debt was apparent. There were significant reductions in time spent awake and in latencies for sleep and stage 4 sleep. The duration of stage 4 sleep significantly increased during the four successive restricted-sleep nights, whereas esophageal temperature significantly decreased over the successive days. When heat was added, esophageal temperature decrease was weakened, and the significant increase in stage 4 duration seen at 20 degrees C was not found. The findings suggest that the heat load imposed in our experimental condition has a suppressive effect on sleep stage 4 increase, which is induced by sleep restriction. The hypothesis that an increase in this sleep stage serves as a mechanism for energy conservation should be also considered.

Adult↗

Six-hour selective REM sleep deprivation increases the expression of the galanin gene in the hypothalamus of rats.

The effect of short-term selective REM sleep deprivation (RSD) on the gene expression of galanin in the rat hypothalamus was examined using in situ hybridization histochemistry. Monitoring an electroencephalogram (EEG) and electromyogram (EMG) on an on-line computer screen, as the RSD rats entered REM sleep, they were gently stroked on their backs using a brush to wake them during the RSD period. Galanin mRNA levels in the preoptic area (POA) were significantly increased by RSD for a period of 6 h. RSD had no significant effect on the mRNA levels of corticotrophin-releasing factor (CRF), arginine vasopressin (AVP), oxytocin (OXT) or orexins. These results suggest that 6-h selective RSD may not be sufficient to induce the activation of the hypothalamo-pituitary adrenal axis, and that the expression of the galanin gene in the hypothalamus reacts more readily against the loss of REM sleep in comparison to other hypothalamic neuropeptides such as arginine vasopressin, oxytocin and orexins.

Animals↗

Psychological effects of Neurotropin in man under normal conditions and after sleep deprivation: a double-blind placebo study.

Psychological effects of Neurotropin--a widely used analgesic in Japan--have been evaluated in a double blind cross-over study on volunteers belonging to the nursing staff of a hospital under sleep deprivation or not. Each subject was asked to record his feelings by self-assessment on scales registering the following states: fatigue-/rest+, mental stress-/relaxation+, cold sensation-/comfort+, dissatisfaction-/satisfaction+. Neurotropin was shown to be devoid of demonstrable psychological effects in the subjects under normal sleeping conditions. After sleep deprivation, Neurotropin globally determined significantly more psychological evolutions towards positives+ and less towards negative- mood than inactive placebo. From the self-assessed feelings, euphoria was unaffected, whereas Neurotropin significantly reduced fatigue and improved relaxation and comfort. These results are compared with the observations made on animals submitted to Specific Alternation of Rhythm in Temperature (SART) where Neurotropin relieves such symptoms as hyperalgesia. This model for experimental pain study corresponds to a depletion of brain serotonin and catecholamines. The effects of Neurotropin on exhausted volunteers could, as in the SART model, be due to an inhibition of monoaminergic depletion. The relevance of this finding to some association of chronic pain and psychogenic factors is to be considered.

Adult↗

Rapid-eye-movement sleep deprivation inhibits clonidine-induced sedation in rats.

The effects of 24 and 48 h of rapid-eye-movement sleep deprivation (REMD) on clonidine-induced sedation and [3H]clonidine binding to cortical membranes were studied in rats. REMD did not affect the exploratory behaviour (ambulation, rearing + peeping) of normal rats. The sedative effect of clonidine (0.2 mg/kg s.c.) on the rearing + peeping behaviour of rats was inhibited by REMD. [3H]Clonidine binding in the cerebral frontal cortex remained unaffected. The results are discussed in terms of changes in the noradrenergic system.

Animals↗

Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation.

Partial sleep deprivation (PSD) has a profound and rapid effect on depressed mood. However, the transient antidepressant effect of PSD - most patients relapse after one night of recovery sleep - is limiting the clinical use of this method. Using a controlled, balanced parallel design we studied, whether repetitive transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able to prevent this relapse. 20 PSD responders were randomly assigned to receive either active or sham stimulation during the following 4 days after PSD. Active stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD up to 4 days. This finding indicates that rTMS is an efficacious method to prevent relapse after PSD.

Adult↗

Intracranial self-stimulation after paradoxical sleep deprivation induced by the platform method in rats.

Lateral hypothalamic intracranial self-stimulation was studied before and after paradoxical sleep deprivation (PSD) induced by the platform method. Rats were assigned to two counterbalanced groups where the sequence order of experimental (small platform) and control (large platform) treatments was permuted. In contrast with previous findings significant changes in the response rates for intracranial self-stimulation were not observed after PSD. Ineffectiveness and nonspecific effects of the treatment are ruled out as the cause for our findings. An hypothesis is suggested that the effect of PSD upon intracranial self-stimulation could be dependent of the brain electrode location.

Animals↗

Sleep deprivation by the "flower pot" technique and spatial reference memory.

This study investigated whether paradoxical, or rapid eye movement (REM), sleep deprivation (SD) affected spatial memory. SD was induced in male Wistar rats by housing them on small platforms over water. They fell into the water if they lost muscle tone. Controls were either housed in tanks with large platforms (TC) or in normal cages (CC). All rats had free access to food and water. Each day they were tested in a place-learning set task using a Morris water maze. The rats were released from 6 different starting points (sets) and allowed 2 min to find a submerged platform. Two trials were conducted from each starting point. SD caused a significant decrement in performance in Trial 1 from Day 2. By Day 4, when distance swum to find the platform was plotted against set, area under the curve was doubled in SD compared to that in TC and CC rats, indicating a significant impairment in reference spatial memory. There was no consistent effect on working memory, indicated by Trial 2. SD caused weight loss and increased serum corticosterone compared to that in CC rats. There were no differences in concentrations of hypothalamic, hippocampal, or cortical catecholamines or their metabolites. Serotonin metabolism was elevated in the hypothalamus and hippocampus in SD rats. These results indicate that SD induced in rats housed on small platforms causes a substantial impairment of reference memory. The memory deficit may not be specific to SD because the rats are physically stressed and lose some nonREM sleep when housed in these conditions.

Animals↗

SPS-B, a physiological sleep regulator, from the brainstems of sleep-deprived rats, identified as oxidized glutathione.

We previously reported regarding the "sleep-promoting substance (SPS)," which was isolated from the brainstem extract of sleep-deprived rats, the existence of multiple active components including uridine and SPS-B. Intracerebroventricular infusion of crude SPS-B exhibited significant enhancing effects on both slow wave sleep and paradoxical sleep in unrestrained rats. Further investigation of SPS-B has resulted in its final identification as oxidized glutathione (GSSG, gamma-glutamylcysteinylglycine disulfide). Authentic GSSG similarly administered in rats also significantly enhanced sleep which was indistinguishable from normal physiological sleep. We propose GSSG as a candidate endogenous sleep substance.

Animals↗

Effect of physical exercise and sleep deprivation on plasma androgen levels: modifying effect of physical fitness.

The responses of plasma testosterone (T), sex hormone-binding globulin (SHBG) binding capacity, androstenedione (A), and luteinizing hormone (LH) to 21 km of marching exercise and to sleep deprivation stress were studied in army recruits. The effect of physical fitness on the exercise responses was evaluated, cross-sectionally, by comparing the stress responses in 11 fit and 11 less fit subjects, and, longitudinally, in 11 subjects after 4 months of physical training. The submaximal marching exercise did not significantly alter the plasma hormone levels compared to the control day levels. The fit subjects had a tendency toward smaller decreases in the mean plasma T and T/SHBG ratio during both control and exercise days than the less fit subjects. After 4 months of conditioning, the mean plasma T and T/SHBG ratio tended to decrease less during both control and exercise days, which was more evident in the well-conditioned subjects. The exercise caused a decrease in mean plasma LH, especially in the less fit subjects. After sleep deprivation stress, the morning levels of plasma T, A, and LH were significantly depressed, as a result of which the normal diurnal variation of the hormones disappeared.

Androgens↗

[Neurophysiologic aspects of sleep deprivation in depression].

Study of EEG in 45 patients, suffering from endogenic and psychogenic depression, in the state of rest, in mental and emotional loads, SGR, orienting reaction and night sleep before and after a course of sleep deprivation has shown that neurophysiological shifts in the cycle alertness-sleep have one direction. The weakening of depression was accompanied by rather unidirected alterations of neurophysiological relations, which testified to the normalization of biological periods of the organism.

Bipolar Disorder↗