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Influence of paradoxical sleep deprivation and cocaine on development of spontaneous penile reflexes in rats of different ages.

Recent studies have established that paradoxical sleep deprivation (PSD) and cocaine administration induce genital reflexes (penile erection and ejaculation) in adult and old rats. To determine whether the same effects would induce spontaneous genital reflexes in rats of different ages (30-90 days old), we administered with cocaine (7 mg/kg) or saline to rats after a 4-day period of PSD, or at the equivalent time-point in control animals, and penile erection and ejaculation were then evaluated. In PSD rats administered cocaine, erection was observed from 30 days old to 90 days old, when both genital reflexes reached a peak. Animals submitted to PSD and saline injection showed erection from 60 to 90 days old. None of the control (saline and cocaine) groups of any age displayed these behaviors. The effects of PSD on steroid hormone levels showed that, although testosterone levels increased with age, PSD caused a marked decrease in testosterone at all ages evaluated. Progesterone and corticosterone levels were higher in PSD groups than in the respective control groups. These findings suggest that the interaction of PSD and cocaine probably enhances dopaminergic transmission in the brain and may accelerate the development of genital reflexes in male rats.

Age Factors↗

Effects of sleep deprivation on serotonin function in depression.

There is considerable evidence that antidepressant treatments enhance serotonin (5-HT) function. In order to evaluate whether sleep deprivation (SD) produces alterations in 5-HT function, the increase in prolactin (PRL) produced by intravenous tryptophan (TRP) was assessed in depressed patients following SD and undisturbed sleep (US). Eleven depressed patients received mood ratings and TRP infusions after either SD or US, 1 week apart. In five women, but not six men, the TRP-induced PRL rise was markedly enhanced after SD compared to US. Mood score changes were not significantly different between US and SD and there was no significant relationship of mood changes to the TRP induced PRL response. The data suggests that SD produces an increase in 5HT function in female depressed patients. The lack of identified SD-induced changes in 5-HT function in men may be due to lower sensitivity of the TRP-induced PRL rise in depressed men than women.

Adolescent↗

Sleep deprivation or postnatal depression in later infancy: separating the chicken from the egg.

OBJECTIVES: To explore the association between maternal distress and depression in the first years of a newborn's life and the child's sleeping behaviour and problems associated with this behaviour. To asses the effectiveness of an outpatient-based individualised behaviour modification programme to modify children's sleep behaviour and to decrease levels of maternal distress and depression. METHOD: Families were referred to an outpatient childhood sleep problems clinic. Intervention consisted of an individualised management programme including recognised modes of child sleep behaviour management ('controlled crying', 'cold turkey,' rewards) together with occasional use of short-term (less than 2 weeks) tapering dose sedating medication for the child. Two months after the initial contact with the clinic, families completed a second questionnaire collating similar data to that collected at time of enrolment. RESULTS: A total of 114 consecutive families referred to the clinic provided initial data. Follow-up questionnaires were returned by 70 (61%). Significant change was recorded in children's sleep parameters including reduction in mean number of night time awakenings (4.1-1.3, P < 0.001), proportion of children requiring longer than 30 min to settle at night (49% to 21%, P < 0.01) and in the proportion of children settling after 8 pm (51% to 33%, P < 0.01). Sleep problem rating on a 0-10 scale decreased from a mean of 8.1-3.1 (P < 0.001). On initial assessment, 40% of mothers had Edinburgh Postnatal Depression Scale (EPNDS) scores greater than 12 (screening cut-off point). At repeat assessment, 4.3% had scores greater than 12. The mean score on the EPNDS fell from 11.2 to 5.8 (P < 0.001). CONCLUSIONS: An outpatient-based individualised approach to modifying children's problematic sleep behaviour using recognised behaviour management techniques is effective. Modification of problematic childhood sleep behaviour is associated with significant improvement in maternal mood. Given the high incidence of childhood sleep problem and diagnosed postnatal depression, it is likely significant numbers of mothers being diagnosed as having postnatal depression are suffering the effects of chronic sleep deprivation. Management of postnatal mood disorder and childhood sleep behaviour must occur with due recognition to their close association.

Adult↗

A turning point for mood during sleep deprivation therapy--does it exist?

The investigated patients did not demonstrate a common turning point of mood in the night of sleep deprivation therapy. The antidepressant effect of SD does not occur before the end of the night of SD. No critical period for changes of mood between 2 a.m. and 4 a.m. were found. Retrospective interviews of patients concerning the completed night of SD are problematic.

Adult↗

Sleep deprivation in the rat: XVI. Effects in a light-dark cycle.

To avoid a possible confound between the effects of sleep loss and disturbed circadian rhythms in previous studies of total sleep deprivation (TSD) by the disk-over-water method, TSD rats and their yoked control (TSC) rats had been maintained in constant light both before and during the experiment. With circadian rhythms of both groups flattened by constant light, group differences in outcome measures could be attributed to sleep loss. However, the constant light control entailed the possibility that the sleep loss effects might obtain only in constant light. To evaluate this possibility, three TSD-TSC rat pairs maintained on a 12 hour light: 12 hour dark (LD) schedule were studied. TSC rats showed only minor changes during the deprivation period. As in previous studies, TSD rats showed increased food intake; decreased weight; increased energy expenditure; debilitated appearance; lesions on the tail and paws; an initial increase followed by a large decrease in body temperature; impending death; and recovery sleep, which featured large, selective, sustained rebounds of paradoxical sleep and a reversal of all observed TSD-induced changes. Thus, TSD produced the same changes during an LD schedule as during constant light. The amplitude of the diurnal body temperature rhythm declined over the course of TSD and then almost completely recovered during the first day of recovery sleep. The decline was interpreted as the result of deprivation-induced thermoregulatory changes.

Animals↗

Effect of sleep and sleep deprivation on serotonergic neurotransmission in the hippocampus: a combined in vivo microdialysis/EEG study in rats.

Brainstem serotonergic neurotransmission is implicated in sleep regulation. However, the role of serotonin (5-HT) in forebrain regions in sleep-wake mechanisms is still unclear. Here, we have investigated, using a combined in vivo microdialysis/electroencephalogram method, the relationship between hippocampal 5-HT levels and sleep-wake behaviour in the rat. A clear-cut relationship was found between hippocampal 5-HT levels and vigilance state. The highest levels of 5-HT were observed during wakefulness, whereas a progressive decrease of 5-HT going from nonrapid eye movement sleep to rapid eye movement sleep was found. Sleep deprivation (SD) causes a transient enhancement of mood in depressed patients. Given the putative role of 5-HT in the aetiology of depression and the therapeutical efficacy of selective serotonin reuptake inhibitors in this illness, we also studied hippocampal 5-HT during 4 h of SD and during the subsequent recovery period. During the whole SD period, 5-HT levels were elevated substantially when compared to 5-HT levels during basal wakefulness. However, no changes in 5-HT levels and the relationship between hippocampal 5-HT and vigilance state were found during the subsequent recovery period. As SD is a potentially stressful experience and glucocorticoids are involved in the regulation of serotonergic neurotransmission and sleep, we investigated the effects of SD on free corticosterone levels. SD caused a marked rise in free corticosterone levels. However, the effects of SD on 5-HT seem not to be mediated by this hormone, because adrenalectomy did not affect the rise in hippocampal 5-HT during SD. We hypothesize that the elevated hippocampal 5-HT levels during SD may participate in the transient mood enhancing properties of forced wakefulness observed in depressed patients.

Adrenalectomy↗

The influence of physical activity and posture on the antidepressant effect of sleep deprivation in depressed patients.

A possible role of the factors 'physical activity' and 'posture' in the antidepressant effect of a total night's sleep deprivation (TSD) was investigated in 30 patients with major depressive disorder. Fifteen patients underwent TSD under 'conventional' conditions, while the other 15 were kept in bed during TSD but were not permitted to sleep. There was no significant difference between the antidepressant effects of TSD in the two groups. This result suggests that it is wakefulness itself rather than changes in physical activity or posture that is involved in the mechanism of the antidepressant action of TSD.

Adult↗

[Nocturnal polygraphic studies during the treatment of depressed patients with sleep deprivation].

In 33 patients with endogenic and psychogenic depression treated by a course of total agrypnotic therapy, the time-course of the clinical and psychological parameters was compared with the findings provided by polygraphic examinations of night sleep. Sleep deprivation lessened depression by regulating the pattern of sleep in depressive patients which was expressed both in its deepening and the improvement of its total and cyclic organization. The efficacy of the agrypnotic therapy was more effective in cases when the quantitative parameters of sleep were disrupted less severely and when gross pathological changes of its general pattern predominated. The study confirms the homogeneity of the neurophysiological and biochemical cerebral processes responsible for the emotional state of the person and the integration of his or her sleep.

Adult↗

Effects of total sleep deprivation on urinary cortisol, self-rated arousal, and mood in depressed patients.

The possibility that the clinical response to total sleep deprivation (TSD) is mediated by dimensions of arousal was investigated in a group of 16 depressed patients. Self-reports of activation, stress, and mood were assessed 3 days before, during, and 2 days after TSD. Urinary cortisol excretion and responses to the dexamethasone suppression test (DST) were also measured. TSD increased cortisol excretion in depressed patients and advanced the time of the maximal excretion of cortisol. No such changes have been reported for normal subjects. Neither the increased excretion nor the time shift was related to the mood response to TSD. The DST results were also unrelated to this response. Indications that the mood response to TSD may be mediated by dimensions of arousal are the significant relationships between this response and the responses of subjective stress and activation to TSD. The TSD-induced cortisol increase was not related to the subjective arousal response to TSD. The increased cortisol excretion itself could be predicted by the averaged baseline levels of subjective stress: the lower the stress levels before TSD, the larger the cortisol response to TSD.

Adult↗

Total sleep deprivation and novelty processing: implications for frontal lobe functioning.

OBJECTIVE: Mounting evidence suggests that the frontal lobes are particularly vulnerable to total sleep deprivation (TSD). Detection of novelty involves the frontal lobes. The presentation of rare, novel stimuli elicits an event-related potential (novel P3), which maximizes over anterior regions of the scalp. We hypothesized that TSD would impair novelty detection, resulting in a smaller novel P3 over the frontal region, with a topographic shift toward posterior areas. METHODS: An auditory novelty oddball task was administered to a TSD group after 36 h of waking and again following recovery sleep, and to a control group after 12 h of waking. EEG was recorded from Fz, Cz and Pz. RESULTS: A large anterior P3 was elicited in the control group. In the TSD group, this novel P3 was smaller at Fz. A later novel positivity appeared in parietal areas. The novel P3 returned to baseline levels and the late novel P3 was difficult to observe following recovery sleep. CONCLUSIONS: TSD appears to compromise the usual automatic detection of novelty probably due to frontal deactivation. Participants may compensate by relying on posterior brain mechanisms involving active memory comparison. The late novel P3 component may also reflect a secondary effortful attempt to encode and to categorize novel stimuli. SIGNIFICANCE: This study suggests that TSD may compromise cognitive functioning in different regions of the brain. The detection of novelty, probably mediated by the frontal lobes, is particularly at risk.

Acoustic Stimulation↗

Hormonal and behavioural responses of paradoxical sleep-deprived rats to the elevated plus maze.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is observed immediately after 96 h of paradoxical sleep (PS) deprivation. However, when individually or group PS-deprived rats are challenged with a mild stressor, they exhibit a facilitation of the corticosterone response, and a faster return to basal levels than control rats. Because the housing condition influences coping behaviour, we tested whether the type of PS deprivation (individually or in group) influenced anxiety-like behaviour in the elevated plus-maze and the accompanying adrenocorticotropin (ACTH) and corticosterone responses. Individually (I-DEP) or group deprived (G-DEP) rats and their appropriate control groups were either killed immediately after 96 h of sleep deprivation (time-point 0 or 'basal') or exposed to a 5-min test on the elevated plus maze and sampled 5, 20 or 60 min after test onset. Control of I-DEP rats showed reduced locomotor activity and augmented anxiety-like behaviour, replicating the effects of social isolation. Although I-DEP rats exhibited higher motor activity than cage control rats, these groups did not differ in regard to the percentage of entry and time spent in the open arms. G-DEP rats, in turn, ambulated more, entered and remained longer in the open arms, exhibiting less anxiety-like behaviour. PS-deprived rats exhibited higher ACTH and corticosterone 'basal' secretion than control rats. For all groups, peak ACTH secretion was reached at the 5-min time-point, returning to unstressed basal levels 60 min after the test, except for G-DEP rats, which showed a return at 20 min. Peak levels of corticosterone occurred at 5 min for PS-deprived groups and at 20 min for control groups. G-DEP rats showed a return to 'basal' unstressed levels at 20 min, whereas the I-DEP and control groups did so at 60 min. A negative correlation between exploration in the open arms and hormone concentrations was observed. These data indicate that housing condition influences the subsequent behaviour of PS-deprived rats in the EPM which, in turn, seems to determine the secretion profile of ACTH and corticosterone in response to the test.

Adrenocorticotropic Hormone↗

Effects of adaptogens on granulocytopoiesis during paradoxical sleep deprivation.

We studied the effects of extracts from Siberian ginseng, Rhodiola rosea, bergenia, and ginseng (G115) and pantohematogen on granulocytopoiesis after paradoxical sleep deprivation. The effects of adaptogens on the blood system were most pronounced during hyperplasia of granulocytopoiesis. Natural preparations were divided into groups depending on their activity. Extracts of Siberian ginseng and Rhodiola rosea did not modulate granulocytopoiesis. Ginseng G115 extract suppressed granulocytopoiesis. Bergenia extract and pantohematogen produced ambiguous effects on the granulocytic hemopoietic stem.

Allergens↗

Retrograde amnesia: electroconvulsive shock effects after termination of rapid eye movement sleep deprivation.

Mice that were deprived of rapid eye movement sleep for 2 days immediately after one-trial training in an inhibitory avoidance task and were given an electroconvulsive shock after deprivation displayed retrograde amnesia on a retention test given 24 hours later. Electroconvulsive shock produced no amnesia in comparable groups of animals that were not deprived of rapid eye movement sleep.

Amnesia↗

Mechanisms underling the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation.

We studied the effects of adaptogens extracts of Siberian ginseng, Rhodiola rosea, bergenia, and ginseng and pantohematogen, on erythropoiesis after paradoxical sleep deprivation. Adaptogens stimulated bone marrow erythropoiesis in the early stage, but decreased the count of bone marrow erythrokaryocytes 3-7 days after treatment. The effect of adaptogens on erythropoiesis is associated with modulation of the state of brain neurotransmitter systems followed by changes in functional activity of cells in the hemopoiesis-inducing microenvironment.

Animals↗

[Sleep deprivation as a method of treating endogenous depression].

Forty-six patients with various forms of endogenous depression were treated by night sleep deprivation (NSD) which was used as the cardinal method of treatment. A single session of NSD induced a considerable clinical improvement lasting 2-3 days in the majority of patients. Repetition of the procedure (3-6 times with a 2-3 day interval) led to a significant and stable clinical improvement in 32 of the 46 patients. The highest effect of treatment was observed in such symptoms as depression and suicidal tendencies, whereas in patients with vital anxiety, the efficacy of NSD was considerably lower. Individuals with the duration of the phase under one month and the greatest reduction of the symptomatology after the recovery night showed the greatest response to the treatment. Favourable prognostic signs included such symptoms as psychomotor inhibition, lassitude and apathy, although the tempo of their reduction in the process of treatment considerably lagged behind improvement in the general mood, sleep and regress of autonomous disorders. Activation of the noradrenergic system is assumed to be one of the main mechanisms of NSD action.

Adult↗

Aerobic fitness and hormonal responses to prolonged sleep deprivation and sustained mental work.

This study examined the influence of aerobic fitness on the responses of selected hormones to the combined stressors of sleep deprivation (SD) and sustained mental work. Six aerobically high fit (HF) (VO2max greater than 50 ml.kg-1.min-1) and six average fit (AF) (VO2max less than 40 ml.kg-1.min-1) female subjects were subjected to a period of sleep loss of 60 h during which time they performed sustained mental tasks with no physical activity component. Venous blood samples were drawn every 12 h at 1330 hours and 0130 hours and plasmas analyzed for cortisol, growth hormone (hGH), prolactin, thyroxine (T4), triiodothyronine (T3), and reverse-triiodothyronine (rT3). For cortisol, both the HF and AF groups exhibited the normal high-daytime and low-nighttime pattern of secretion, with levels increasing significantly as the duration of SD increased. The normal elevations of hGH and prolactin levels during normal sleep were suppressed during SD. No significant fitness effects were found for cortisol, hGH, and prolactin responses. Plasma levels of T4, T3, and rT3 increased significantly during SD, with highly fit subjects exhibiting higher levels of these hormones than those of average fitness. We suggest that aerobic fitness may influence the peripheral metabolism of T4 during SD, but that aerobic fitness does not influence the regulation of the classical stress hormones during SD.

Adult↗

Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation.

BACKGROUND: Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known. METHODS: In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression. RESULTS: In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor alpha was significantly greater compared with morning levels following uninterrupted sleep. In addition, sleep loss induced a more than 3-fold increase in transcription of interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha messenger RNA. Bioinformatics analyses suggested that the inflammatory response was mediated by the nuclear factor kappaB inflammatory signaling system as well as through classic hormone and growth factor response pathways. CONCLUSIONS: Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.

Adult↗