Significant Increase In Slow Wave Sleep Research Articles

Effect of Inactivation of Prefrontal Cortex on Sleep-Wake States in Rat

There is a large body of literature to support subcortical regulation of sleep-wake states, but there have been limited studies to investigate the role of cortex in sleep-wake regulation. Previously, we have demonstrated that cholinergic stimulation of prefrontal cortex can reverse general anesthesia and promote wakefulness in unanesthetized rats, and there is emerging evidence to suggest that the prefrontal cortex might be a critical node in arousal state control. To better understand the direct role of prefrontal cortex in the regulation of sleep-wake states, we quantified the effect of prefrontal cortex inactivation, via local tetrodotoxin (156 μM) infusion, on sleep architecture. Under surgical isoflurane anesthesia, adult Sprague Dawley rats (n=7 male) were instrumented with electrodes to record electroencephalogram (EEG) from frontal and parietal cortices, and electromyogram (EMG) from dorsal nuchal muscles. In addition, a bilateral guide cannula was implanted aimed at the medial prefrontal cortex for tetrodotoxin infusion. After at least a week of post-surgical recovery and conditioning to the recording chambers, rats received bilateral microinjection (500 nL) of either 156 μM tetrodotoxin or 0.9% saline (vehicle control). The tetrodotoxin and 0.9% saline infusions were performed 30-minutes before the start of lights-OFF period (8:00 pm) after which EEG and EMG data were recorded for 24h across dark and light cycles. The EEG and EMG data were manually scored (SleepSign, Kissei Comtec Inc.) in 4-second intervals into wakefulness, slow-wave sleep, and rapid eye movement sleep, and then averaged in 3h bins across 24h recording period. A linear mixed model was used to compare the changes in percent time spent in each state, mean duration per episode for each state, and mean number of episodes for each state, between the vehicle control and tetrodotoxin-infusion sessions. Inactivation of prefrontal cortex via tetrodotoxin infusion produced long-lasting statistically significant increase in slow-wave sleep (p<0.05 for 0-3h, 4-6h, 7-9h, 10-12h, 13-15, 16-18, 22-24) and decrease in wakefulness (p<0.05 for 0-3h, 4-6h, 10-12h) and rapid eye movement sleep (p<0.05 for 7-9h, 10-12h, 13-15h). These data further support a causal contribution of prefrontal cortex in regulating arousal states. This work was supported by the National Institutes of Health (Bethesda, MD, USA) grant (R01 GM111293) to GAM and DP, and funding from the Department of Anesthesiology, University of Michigan Medical School, Ann Arbor. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep

Environmental temperature can strongly affect sleep. The habitual sleep phase is usually located between evening decline and morning rise of the circadian rhythm of core body temperature (CBT). However, the thermophysiological mechanisms promoting or disturbing sleep are not yet fully understood. The purpose of this study was to examine the effects of a high heat capacity mattress (HHCM) on CBT, skin temperatures and sleep in comparison to a conventional low heat capacity mattress (LHCM). Based on the higher heat capacity of HHCM an increase in conductive body heat loss enhances the nocturnal decline in CBT can be expected. Based on previous findings this may then be accompanied by an increase in slow wave sleep (SWS).The mattresses were studied in a randomized single-blind crossover design in fifteen healthy young men (Age: 26.9±2.1yr, BMI: 22.2±0.4kg/m2) by overnight in laboratory standard video-polysomnography in a temperature stabilized setting. CBT, room temperature, and skin and mattress surface temperatures were continuously recorded in order to get information about inner and outer body heat flow. Additionally, subjective sleep quality was estimated by visual analogue scale.In comparison to LHCM sleep on HHCM exhibited a selective increase in SWS (16%, p<0.05), increased subjective sleep quality and sleep stability [reduced cyclic alternating pattern (CAP) rate; 5.3%, p<0.01]. Additionally, analyses of the sleep stages showed in the second part of the night a significant increase in SWS and a decrease in REMS. In addition, HHCM induced a greater reduction in CBT (maximally by −0.28°C), reduced the increase in proximal skin temperatures on the back (PROBA; maximally by −0.98°C), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 6.12°C). Thus, the CBT reduction can be explained by an increase in conductive heat loss to the mattress via proximal back skin regions. Regression analysis identified PROBA as the critical variable to predict inner conductive heat transfer from core to shell and SWS.In conclusion, the study expands the previous findings that a steeper nocturnal decline in CBT increases SWS and subjective sleep quality, whereas inner conductive heat transfer could be identified as the crucial thermophysiological variable, and not CBT.

Serotonin control of sleep-wake behavior

Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) functions predominantly to promote wakefulness (W) and to inhibit REM (rapid eye movement) sleep (REMS). Yet, under certain circumstances the neurotransmitter contributes to the increase in sleep propensity. Most of the serotonergic innervation of the cerebral cortex, amygdala, basal forebrain (BFB), thalamus, preoptic and hypothalamic areas, raphe nuclei, locus coeruleus and pontine reticular formation comes from the dorsal raphe nucleus (DRN). The 5-HT receptors can be classified into at least seven classes, designated 5-HT(1-7). The 5-HT(1A) and 5-HT(1B) receptor subtypes are linked to the inhibition of adenylate cyclase, and their activation evokes a membrane hyperpolarization. The actions of the 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptor subtypes are mediated by the activation of phospholipase C, with a resulting depolarization of the host cell. The 5-HT(3) receptor directly activates a 5-HT-gated cation channel which leads to the depolarization of monoaminergic, aminoacidergic and cholinergic cells. The primary signal transduction pathway of 5-HT(6) and 5-HT(7) receptors is the stimulation of adenylate cyclase which results in the depolarization of the follower neurons. Mutant mice that do not express 5-HT(1A) or 5-HT(1B) receptor exhibit greater amounts of REMS than their wild-type counterparts, which could be related to the absence of a postsynaptic inhibitory effect on REM-on neurons of the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT). 5-HT(2A) and 5-HT(2C) receptor knock-out mice show a significant increase of W and a reduction of slow wave sleep (SWS) which has been ascribed to the increase of catecholaminergic neurotransmission involving mainly the noradrenergic and dopaminergic systems. Sleep variables have been characterized, in addition, in 5-HT(7) receptor knock-out mice; the mutants spend less time in REMS that their wild-type counterparts. Direct infusion of the 5-HT(1A) receptor agonists 8-OH-DPAT and flesinoxan into the DRN significantly enhances REMS in the rat. In contrast, microinjection of the 5-HT(1B) (CP-94253), 5-HT(2A/2C) (DOI), 5-HT(3) (m-chlorophenylbiguanide) and 5-HT(7) (LP-44) receptor agonists into the DRN induces a significant reduction of REMS. Systemic injection of full agonists at postsynaptic 5-HT(1A) (8-OH-DPAT, flesinoxan), 5-HT(1B) (CGS 12066B, CP-94235), 5-HT(2C) (RO 60-0175), 5-HT(2A/2C) (DOI, DOM), 5-HT(3) (m-chlorophenylbiguanide) and 5-HT(7) (LP-211) receptors increases W and reduces SWS and REMS. Of note, systemic administration of the 5-HT(2A/2C) receptor antagonists ritanserin, ketanserin, ICI-170,809 or sertindole at the beginning of the light period has been shown to induce a significant increase of SWS and a reduction of REMS in the rat. Wakefulness was also diminished in most of these studies. Similar effects have been described following the injection of the selective 5-HT(2A) receptor antagonists volinanserin and pruvanserin and of the 5-HT(2A) receptor inverse agonist nelotanserin in rodents. In addition, the effects of these compounds have been studied on the sleep electroencephalogram of subjects with normal sleep. Their administration was followed by an increase of SWS and, in most instances, a reduction of REMS. The administration of ritanserin to poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder caused a significant increase in SWS. The 5-HT(2A) receptor inverse agonist APD-125 induced also an increase of SWS in patients with chronic primary insomnia. It is known that during the administration of benzodiazepine (BZD) hypnotics to patients with insomnia there is a further reduction of SWS and REMS, whereas both variables tend to remain decreased during the use of non-BZD derivatives (zolpidem, zopiclone, eszopiclone, zaleplon). Thus, the association of 5-HT(2A) antagonists or 5-HT(2A) inverse agonists with BZD and non-BZD hypnotics could be a valid alternative to normalize SWS in patients with primary or comorbid insomnia.

P.8.a.025 Therapeutic contact through Internet. Discussion of the theoretical and technical possibilities of realization therapy

Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) functions predominantly to promote wakefulness (W) and to inhibit REM (rapid eye movement) sleep (REMS). Yet, under certain circumstances the neurotransmitter contributes to the increase in sleep propensity. Most of the serotonergic innervation of the cerebral cortex, amygdala, basal forebrain (BFB), thalamus, preoptic and hypothalamic areas, raphe nuclei, locus coeruleus and pontine reticular formation comes from the dorsal raphe nucleus (DRN). The 5-HT receptors can be classified into at least seven classes, designated 5-HT1–7. The 5-HT1A and 5-HT1B receptor subtypes are linked to the inhibition of adenylate cyclase, and their activation evokes a membrane hyperpolarization. The actions of the 5-HT2A, 5-HT2B and 5-HT2C receptor subtypes are mediated by the activation of phospholipase C, with a resulting depolarization of the host cell. The 5-HT3 receptor directly activates a 5-HT-gated cation channel which leads to the depolarization of monoaminergic, aminoacidergic and cholinergic cells. The primary signal transduction pathway of 5-HT6 and 5-HT7 receptors is the stimulation of adenylate cyclase which results in the depolarization of the follower neurons. Mutant mice that do not express 5-HT1A or 5-HT1B receptor exhibit greater amounts of REMS than their wild-type counterparts, which could be related to the absence of a postsynaptic inhibitory effect on REM-on neurons of the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT). 5-HT2A and 5-HT2C receptor knock-out mice show a significant increase of W and a reduction of slow wave sleep (SWS) which has been ascribed to the increase of catecholaminergic neurotransmission involving mainly the noradrenergic and dopaminergic systems. Sleep variables have been characterized, in addition, in 5-HT7 receptor knock-out mice; the mutants spend less time in REMS that their wild-type counterparts. Direct infusion of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan into the DRN significantly enhances REMS in the rat. In contrast, microinjection of the 5-HT1B (CP-94253), 5-HT2A/2C (DOI), 5-HT3 (m-chlorophenylbiguanide) and 5-HT7 (LP-44) receptor agonists into the DRN induces a significant reduction of REMS. Systemic injection of full agonists at postsynaptic 5-HT1A (8-OH-DPAT, flesinoxan), 5-HT1B (CGS 12066B, CP-94235), 5-HT2C (RO 60-0175), 5-HT2A/2C (DOI, DOM), 5-HT3 (m-chlorophenylbiguanide) and 5-HT7 (LP-211) receptors increases W and reduces SWS and REMS. Of note, systemic administration of the 5-HT2A/2C receptor antagonists ritanserin, ketanserin, ICI-170,809 or sertindole at the beginning of the light period has been shown to induce a significant increase of SWS and a reduction of REMS in the rat. Wakefulness was also diminished in most of these studies. Similar effects have been described following the injection of the selective 5-HT2A receptor antagonists volinanserin and pruvanserin and of the 5-HT2A receptor inverse agonist nelotanserin in rodents. In addition, the effects of these compounds have been studied on the sleep electroencephalogram of subjects with normal sleep. Their administration was followed by an increase of SWS and, in most instances, a reduction of REMS. The administration of ritanserin to poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder caused a significant increase in SWS. The 5-HT2A receptor inverse agonist APD-125 induced also an increase of SWS in patients with chronic primary insomnia. It is known that during the administration of benzodiazepine (BZD) hypnotics to patients with insomnia there is a further reduction of SWS and REMS, whereas both variables tend to remain decreased during the use of non-BZD derivatives (zolpidem, zopiclone, eszopiclone, zaleplon). Thus, the association of 5-HT2A antagonists or 5-HT2A inverse agonists with BZD and non-BZD hypnotics could be a valid alternative to normalize SWS in patients with primary or comorbid insomnia.

Alcohol‐induced sleepwalking or confusional arousal as a defense to criminal behavior: a review of scientific evidence, methods and forensic considerations

An increasing number of criminal cases have claimed the defendant to be in a state of sleepwalking or related disorders induced by high quantities of alcohol. Sleepwalkers who commit violent acts, sexual assaults and other criminal acts are thought to be in a state of automatism, lacking conscious awareness and criminal intent. They may be acquitted in criminal trials. On the other hand, criminal acts performed as the result of voluntary alcohol intoxication alone cannot be used as a complete defense. The alcohol-induced sleepwalking criminal defense is most often based on past clinical or legal reports that ingestion of alcohol directly 'triggers' sleepwalking or increased the risk of sleepwalking by increasing the quantity of slow wave sleep (SWS). A review of the sleep medicine literature found no sleep laboratory studies of the effects of alcohol on the sleep of clinically diagnosed sleepwalkers. However, 19 sleep laboratory studies of the effects of alcohol on the sleep of healthy non-drinkers or social drinkers were identified with none reporting a change in SWS as a percentage of total sleep time. However, in six of 19 studies, a modest but statistically significant increase in SWS was found in the first 2-4 h. Among studies of sleep in alcohol abusers and abstinent abusers, the quantity and percentage of SWS was most often reduced and sometimes absent. Claims that direct alcohol provocation tests can assist in the forensic assessment of these cases found no support of any kind in the medical literature with not a single report of testing in normative or patient groups and no reports of validation testing of any sort. There is no direct experimental evidence that alcohol predisposes or triggers sleepwalking or related disorders. A legal defense of sleepwalking resulting from voluntarily ingested alcohol should be consistent with the current state of art sleep science and meet generally accepted requirements for the diagnosis of sleepwalking and other parasomnias.

Sleep–wake study in an animal model of acute and chronic heat stress

The study of the variations in different parameters of sleep–wake states following exposure to high environmental heat in three different age groups of freely moving rats have been presented in this paper. Each age group of rats was subdivided in three group (i) acute heat stress — subjected to a single exposure for 4 h in the BOD (Biological Oxygen Demand) incubator at 38 °C; (ii) chronic heat stress — exposed for 21 days daily for 1 h in the incubator at 38 °C, and (iii) handling control groups. The polygraphic, analog as well as digital sleep–wake recordings were performed just after the heat exposure from acute stressed rats and on 22nd day from chronic stressed rats. The results of this study revealed that acute exposure to high environmental heat increases sleep efficiency with significant increase in SWS (slow wave sleep) decrease in AWA (awake) time in all three age groups of rats. The increase in SWS and the sleep efficiency in these groups of rats at the cost of decreased time of AWA, indicates the involvement of the hypothalamus in thermoregulatory mechanism to conserve the energy of the body following sudden exposure to high heat. However, the reverse results were observed in the chronic stressed groups of rats, which have occurred mostly owing to the adaptations of the brain functions due to repetitive exposure to environmental heat. In consequence, the present study exhibits that the sleep is highly susceptible to the environmental heat and it is sensitive to the intensity, duration and the mode of exposure.

Chronic benzodiazepine usage and withdrawal in insomnia patients

We studied the sleep of patients with insomnia during continuous and very long-term use of benzodiazepines (BZDs), and after withdrawal. A group of 25 patients (mean age 44.3±11.8 years) with persistent insomnia, who had been taking BZDs nightly for 6.8±5.4 years was selected. The control group was comprised of 18 age-matched healthy individuals. Sleep stage parameters were analyzed during Night 1 (while taking BZDs), Night 2 (first night after completing BZD withdrawal), and Night 3 (15 days after gradual BZD withdrawal). Sleep data for control subjects was monitored in parallel. Sleep EEGs of the patients were analyzed using Period Amplitude Analysis (PAA), during Nights 1 and 3 only. During BZD use, a significant reduction of Total Sleep Time (TST) and increased sleep latency were found in the insomniac group when compared to controls. We found an increase in stage 2 non-REM (NREM) sleep, and a reduction in Slow Wave Sleep (SWS) when comparing to night 3 (after withdrawal). Sleep EEGs analysis showed an increase in sigma band and decrease in delta count in stages 2, 3, 4 NREM and REM sleep in the BZD group when comparing to night 3 (after withdrawal). During the BZD withdrawal period, six out of nine subjects taking lorazepam failed withdrawal. In the remaining 19 subjects, gradual withdrawal of BZDs was associated with immediate worsening of nocturnal sleep, as indicated by sleep parameters. However, 15 days after withdrawal (Night 3), some of the sleep structure parameters of patients were not significantly different from baseline (while taking BZDs), except for a significant increase in SWS and in delta count throughout most sleep stages, and a decrease in stage 2 NREM sleep. These values were not different from those shown by control subjects. REM sleep parameters showed no significant variation across the experimental conditions. Subjective sleep quality was significantly improved on Night 3 compared with Night 1. Conclusions: Chronic intake of BZDs may be associated with poor sleep in this population. A progressive 15-day withdrawal did not avoid an immediate worsening of sleep parameters. But at the end of the protocol, SWS, delta count, and sleep quality were improved compared to those recorded during the chronic BZD intake, despite the lack of change in sleep efficiency.

Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study.

The principal component of marijuana, delta-9-tetrahydrocannabinol increases sleep in humans. Endogenous cannabinoids, such as N-arachidonoylethanolamine (anandamide), also increase sleep. However, the mechanism by which these molecules promote sleep is not known but might involve a sleep-inducing molecule such as adenosine. Microdialysis samples were collected from the basal forebrain in order to detect levels of adenosine before and after injection of anandamide. Rats were implanted for sleep studies, and a cannula was placed in the basal forebrain to collect microdialysis samples. Samples were analyzed using high-performance liquid chromatography. Basic neuroscience research laboratory. Three-month-old male F344 rats. At the start of the lights-on period, animals received systemic injections of dimethyl sulfoxide (vehicle), anandamide, SR141716A (cannabinoid receptor 1 [CB1] antagonist), or SR141716A and anandamide. One hour after injections, microdialysis samples were collected (5 microL) from the basal forebrain every hour over a 20-minute period for 5 hours. The samples were immediately analyzed via high-performance liquid chromatography for adenosine levels. Sleep was also recorded continuously over the same period. Anandamide increased adenosine levels compared to vehicle controls with the peak levels being reached during the third hour after drug injection. There was a significant increase in slow-wave sleep during the third hour. The induction in sleep and the rise in adenosine were blocked by the CB1-receptor antagonist, SR141716A. Anandamide increased adenosine levels in the basal forebrain and also increased sleep. The soporific effects of anandamide were mediated by the CB1 receptor, since the effects were blocked by the CB1-receptor antagonist. These findings identify a potential therapeutic use of endocannabinoids to induce sleep in conditions where sleep may be severely attenuated.

Influence of a 1-h immobilization stress on sleep and CLIP (ACTH 18–39) brain contents in adrenalectomized rats

Basal sleep amounts in adrenalectomized rats (AdX), as compared to intact animals, exhibit a significant increase in slow-wave sleep (SWS), a tendency towards an increase in paradoxical sleep (PS), and circadian rhythms (SWS and PS) flattened in amplitude. An immobilization stress (IS) of 1 h, imposed on AdX rats at the beginning of the dark period, is accompanied by an intense polygraphic waking. Just after the IS, SWS amount become significantly higher than in control rats (+44%/11 h of darkness) whereas significant increases of PS occur only 5–10 h after the IS (+24%/11 h of darkness). A specific radioimmunoassay for CLIP (corticotropin-like intermediate lobe peptide or ACTH 18–39) was performed in biopsies taken either from the nucleus raphe dorsalis (nRD) or the arcuate nucleus (AN). In the nRD, just after the IS, phosphorylated CLIP (Ph-CLIP) concentration exhibits a decreasing tendency, but 4 h later, it increases significantly (+22%, p<0.05). In the AN, Ph-CLIP concentration remains unchanged after the IS as well as 4 h later. These results differ from those previously reported in intact animals also submitted to a 1-h IS, that is, a SWS rebound less marked (+27%/11 h of darkness), a PS rebound more important starting immediately after the IS (+46%/11 h of darkness) and a significant increase in Ph-CLIP occurring just after the end of the restraint. In conclusion, data obtained after a restraint stress either in AdX or in control rats point out the dependence of the PS rebound on the nRD Ph-CLIP concentration.

Intracerebroventricular injection of TNF-alpha promotes sleep and is recovered in cervical lymph.

Recent studies have shown that the central nervous system (CNS) communicates with the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-alpha would not only influence the CNS by promoting sleep but also would be directly transmitted into the peripheral immune system. Five hundred nanograms of 125I-labeled TNF-alpha were injected into the lateral ventricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. 125I-TNF-alpha was measured in lymph nodes and control fat, skin, and muscle tissues 6 h postinjection. 125I-TNF-alpha was detected in the cervical lymphatics within the first 30 min and peaked within 2-3 h. 125I-TNF-alpha counts were elevated in the nodes of the head and neck region. Polysomnographic recordings of four animals showed that TNF-alpha induced a significant increase in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-alpha and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and peripheral immune functions.

Sleep and waking during acute histamine hs agonist BP 2.94 or hs antagonist carboperamide (MR 16155) administration in rats

The present study evaluated the effects of histamine H3 receptor agonist BP 2.94 or H3 receptor antagonist carboperamide (MR 16155) given by oral route on sleep and waking in rats surgically prepared for long-term recordings. BP 2.94 produced a significant increase of slow-wave sleep (SWS) that was related to slight decreases of waking, light sleep, and REM sleep. Carboperamide significantly increased waking and decreased SWS and REM sleep. Pretreatment with carboperamide prevented the effect of BP 2.94 on SWS. It is suggested that the effects of BP 2.94 or carboperamide on sleep and waking could depend on changes in the availability of histamine at the postsynaptic H1 receptor. Alternatively, activation or blockade of the H3 heteroreceptors found in the central catecholamine, indolamine, and acetylcholine nerve endings could inhibit or increase the release of noradrenaline, serotonin, dopamine, and acetylcholine. This would secondarily result in changes of sleep variables.

O-13-1 - Sleep and waking during acute histamine H 3-agonist BP 2.94 or H 3-antagonist carboperamide (MR 16155) administration in rats

The present study evaluated the effects of histamine H3 receptor agonist BP 2.94 or H3 receptor antagonist carboperamide (MR 16155) given by oral route on sleep and waking in rats surgically prepared for long-term recordings. BP 2.94 produced a significant increase of slow-wave sleep (SWS) that was related to slight decreases of waking, light sleep, and REM sleep. Carboperamide significantly increased waking and decreased SWS and REM sleep. Pretreatment with carboperamide prevented the effect of BP 2.94 on SWS. It is suggested that the effects of BP 2.94 or carboperamide on sleep and waking could depend on changes in the availability of histamine at the postsynaptic H1 receptor. Alternatively, activation or blockade of the H3 heteroreceptors found in the central catecholamine, indolamine, and acetylcholine nerve endings could inhibit or increase the release of noradrenaline, serotonin, dopamine, and acetylcholine. This would secondarily result in changes of sleep variables.

Early central nervous system response to HIV infection

To repeat and extend findings suggesting that sleep disturbance, excessive daytime sleepiness, and degraded cognitive-motor abilities may be early markers of central nervous system (CNS) involvement in HIV infection. A controlled, cross-sectional, prospective analysis. Clinical research center at a teaching hospital and a military health research center. Twenty-three HIV-positive (mean CD4+ count, 387 +/- 162 x 10(6)/l) and 13 seronegative men who were Naval personnel or participants of the University of California, San Diego HIV Neurobehavioral Research Center. Nocturnal and daytime sleep electroencephalogram, electromyogram, and electrocardiogram. Simple and complex cognitive-motor performance assessed via computerized tasks. Comparison of sleep parameters based on HIV status, length of time infected, zidovudine use, and CD4+ count indicated that CD4+ T cells > 400 x 10(6)/l were associated with a distortion in nocturnal sleep characterized by increased stages 3 and 4 non-rapid eye movement (i.e., slow-wave) sleep in the latter portion of the night and reduced nocturnal awakenings. HIV-positive patients were no sleepier in the daytime than controls. Cognitive-motor performance revealed deficits in both accuracy and efficiency for HIV-positive patients. Asymptomatic HIV-positive patients with CD4+ counts > 400 x 10(6)/l demonstrate a statistically significant increase in slow-wave sleep during the latter portion of the night and less arousability. CD4+ lymphocyte count in the early phases of HIV infection appears to differentiate between various levels of HIV disease progression with respect to certain CNS measurements of nocturnal sleep and cognitive-motor performance. Sleep structure distortion remains one of the earliest and most consistently replicable physiological signs of HIV infection. This distortion may provide a link to immune function, disease progression, and cognitive-motor disability in HIV infection.

Changes in the rat sleep-wake cycle produced by d,l-β-(1-naphthyl)alanine, a tryptophan analog

The effects of i.p. injections of d,l-β-(1-naphthyl)alanine, a synthetic analog of tryptophan were tested on the rat sleep-waking cycle. Administration of 30, 60 and 120 mg/kg resulted in a significant increase in slow-wave sleep (SWS) and a decrease in paradoxical sleep (PS). These modifications were dose-dependent. These results were compared with those previously obtained with l-tryptophan and several analogs and discussed in relation with possible changes in central serotonergic activity.