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PubMed2006

Features associated with the development of hallucinations in Parkinson's disease.

OBJECTIVE: To identify features related to the development of hallucinations in Parkinson's disease (PD). MATERIALS AND METHODS: Seventy PD patients with hallucinations (group 1) and 60 PD patients without hallucinations (group 2) were evaluated for disease severity, presence of motor complications, rapid eye movement (REM) behavior disorder (RBD), and antiparkinsonian drug profile. The ages at the emergence of hallucinations and duration of disease in group 1 were matched with the ages at the last visit of those in group 2. RESULTS: Disease severity and presence of motor complications were similar in both groups. RBD was more frequently encountered among hallucinators than among non-hallucinators (P = 0.007). The mean duration and daily doses of levodopa and other dopaminergic drugs did not differ in both groups; however, the usage of anticholinergics and amantadine were significantly more frequent in group 2, unexpectedly. CONCLUSIONS: The presence of RBD was significantly more common in hallucinators; however, severity of PD, duration and daily doses of dopaminergic drugs were not associated with the emergence of hallucinations.

Adult↗
PubMed2005

A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress.

The putative effects of a tryptic bovine alphaS1-casein hydrolysate on stress-induced sleep disorders were investigated and their possible link with typical blood stress parameters such as plasma corticosterone concentrations and glycaemia was assessed. Rats were subjected to chronic stress in the form of environmental disturbances, while receiving an oral administration of the alphaS1-casein hydrolysate (CH). Chronic stress significantly reduced sleep duration in control rats during the first 2 days of the stress period, but stress-induced sleep disturbance was prevented in CH-treated rats. Indeed, CH administration allowed the maintenance of slow wave sleep (SWS) duration and even a slight increase in paradoxical sleep (PS) duration in treated rats. Results on plasma corticosterone concentrations and on glycemia values were inconclusive with respect to the implication of the HPA axis in this study. However, the protective effect of the alphaS1-casein hydrolysate on sleep during exposure to our chronic mild stress conditions may be mediated by modulation of the central adrenergic response.

Animals↗
PubMed2004

Behavioral state instability in orexin knock-out mice.

Narcolepsy is caused by a lack of orexin (hypocretin), but the physiologic process that underlies the sleepiness of narcolepsy is unknown. Using orexin knock-out (KO) mice as a model of narcolepsy, we critically tested the three leading hypotheses: poor circadian control of sleep and wakefulness, inadequate activation of arousal regions, or abnormal sleep homeostasis. Compared with wild-type (WT) littermates, orexin KO mice had essentially normal amounts of sleep and wake, but wake and non-rapid eye movement (NREM) bouts were very brief, with many more transitions between all behavioral states. In constant darkness, orexin KO mice had normal amplitude and timing of sleep-wake rhythms, providing no evidence for disordered circadian control. When placed in a new, clean cage, both groups of mice remained awake for approximately 45 min, demonstrating that, even in the absence of orexin, fundamental arousal regions can be engaged to produce sustained wakefulness. After depriving mice of sleep for 2-8 hr, orexin KO mice recovered their NREM and rapid eye movement sleep deficits at comparable rates and to the same extent as WT mice, with similar increases in EEG delta power, suggesting that their homeostatic control of sleep is normal. These experiments demonstrate that the fragmented wakefulness of orexin deficiency is not a consequence of abnormal sleep homeostasis, poor circadian control, or defective fundamental arousal systems. Instead, the fragmented behavior of orexin KO mice may be best described as behavioral state instability, with apparently low thresholds to transition between states.

Animals↗
PubMed1987

Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology.

The diagnosis, treatment, and pathophysiology of obsessive-compulsive disorder (OCD) were examined in a series of studies utilizing psychobiological approaches. Putative biological markers previously reported in depression were studied in this disorder and revealed that on some measures [Dexamethasone Suppression Test and rapid eye movement (REM) latency on sleep electroencephalogram (EEG)], OCD patients resemble those with major depressive disorder (MDD), whereas on others [REM density, platelet serotonin uptake, probably platelet 3H-imipramine binding, and 5-hydroxy-indoleacetic acid (5-HIAA) in cerebral spinal fluid (CSF)] they do not. The relationship between OCD and MDD was further explored in a double-blind, randomized crossover study designed to compare the antiobsessional effects of two tricyclic antidepressants, clomipramine (CMI) and desipramine (DMI), in a nondepressed cohort of OCD patients. CMI was found to have significant antiobsessional effects in this group, whereas in the same patients, DMI lacked therapeutic effects. These results suggest that not all antidepressants are antiobsessive and that some property of CMI, such as its potent serotonergic effects, may be of pathophysiological relevance for OCD. The role of serotonin in this disorder was then tested using the pharmacological challenge strategy. A novel serotonin postsynaptic receptor (5HT-1) agonist, m-chlorophenylpiperazine (m-CPP), was administered orally (0.5 mg/kg) under double-blind, placebo-controlled conditions to OCD patients and controls. In addition, a serotonergic receptor antagonist, metergoline (4 mg), was given to a subset of OCD patients. Relative to healthy volunteers, the OCD patients became significantly more anxious, depressed, and dysphoric after m-CPP administration. Moreover, in the OCD patients, obsessive-compulsive symptoms increased markedly after m-CPP and decreased significantly following metergoline administration. These results demonstrate that agents that bind to the 5HT-1 receptor can acutely affect the symptoms of OCD patients. The striking behavioral effects of these direct postsynaptic receptor ligands and the relative specificity of clomipramine as an antiobsessional agent suggest that serotonergic neurons may play a role in the pathophysiology, as well as mediating the pharmacological reduction, of obsessional symptoms.

Adult↗
PubMed2002

Nightcap: a reliable system for determining sleep onset latency.

Previous studies have demonstrated that the Nightcap home-based sleep-monitoring system can differentiate waking, NREM and REM sleep based on eyelid movements (ELMs) and head movement behavior. The present study aims at determining the reliability of the Nightcap in determining the human sleep onset latency (SOL) as revealed by standard polysomnography (PSG). Four naps were recorded in each of ten normal subjects using both PSG and the Nightcap simultaneously. The Nightcap algorithm scored sleep onset as the first of 4 consecutive 30-sec epochs with less than 5 ELMs. The mean percentage of agreement between the Nightcap and PSG was 93% (k = 0.79), and the average absolute difference was 45 sec (13.3% of SOL(PSG)). SOL(NC) differed by less than 1 min in 85% of onsets. Recordings of EEG activity from 90 sec before and after PSG-identified sleep onsets were subjected to spectral analysis. Changes in spectral power in the theta (4-7 Hz) and alpha (8-12 Hz) frequency bands during the transition into light sleep correlated well with eyelid behavior. However, changes in ELM density predicted sleep onset better than did changes in theta and alpha spectral power. These results suggest that the Nightcap may be a potential alternative to the PSG technique in the assessment of SOL in normal subjects.

Adult↗
PubMed1992

Sleep disturbances in men with asymptomatic human immunodeficiency (HIV) infection.

During the clinical latency phase of human immunodeficiency virus (HIV) disease the central nervous system may be infected and begin to manifest subtle dysfunction. Our early investigations demonstrated persistent alterations in the sleep architecture of HIV-infected asymptomatic men. The major aims of this study were to delineate alterations of sleep architecture in asymptomatic HIV-infected men, to identify and describe sleep behavior complaints and to seek a correlation between objective sleep parameters and subjective complaints of sleep behavior. The study sample consisted of 24 men, 14 HIV-infected and 10 HIV-negative, age-matched controls. The protocol included a comprehensive history and physical, two polysomnograms, urine toxicity, detailed written sleep questionnaire, the Pittsburgh Sleep Quality Index, the Spielberger State-Trait Anxiety Test and the Beck Depression Inventory. Our results indicated that sleep architecture differed from controls in that wakefulness, slow-wave sleep [SWS-stage 3 and 4 nonrapid eye movement (NREM) sleep] and stage rapid eye movement (REM) sleep were more evenly dispersed throughout the night. In particular, SWS was prevalent during the second half of recorded sleep. The observed changes in the NREM/REM cycle could not be explained on the basis of underlying psychopathology. Just as the course of individuals with HIV infection varies, it is expected that sleep abnormalities will vary. Considering the known relationships between NREM stage 3 and 4 and immune system function, it is possible that the observed alterations in the NREM/REM cycle are related to coincident changes in immunologic function. Quantitative measures of NREM sleep, especially SWS and REM sleep, are perhaps of greater significance than relative measures of sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Magnesium involvement in sleep: genetic and nutritional models.

Alterations of peripheral magnesium (Mg) concentration have been reported in association with several behavioral disorders and sleep organization. Blood Mg regulation is under a strong genetic control, whereas brain Mg regulation does not seem to be affected. We have studied peripheral and central levels of Mg and analyzed sleep in two lines of mice selected for low (MGL) and high (MGH) red blood cell (RBC) Mg levels. The same variables were also studied in C57BL/6J mice before and after 3 weeks of Mg deficiency. Whereas blood Mg was highly affected by the selection, brain Mg exhibited only small differences between the two lines. In contrast, Mg deficiency strongly decreased both central and peripheral Mg levels. Sleep analysis indicated that in both models the amount of paradoxical sleep was lower in mice with higher Mg levels. The amplitude of daily variation in sleep and slow-wave sleep delta power was markedly decreased in MGH line. Quantitative electroencephalogram (EEG) analysis also revealed a faster theta peak frequency in MGH mice, irrespective of behavioral states. Central Mg showed significant correlations with the amount of paradoxical sleep and sleep consolidation. However, because the direction of these correlations was not consistent, it is concluded that optimal, (physiological) rather than high or low, Mg levels are needed for normal sleep regulation.

Animals↗
PubMedDate not supplied

Sleep as a mediator of the stress-immune relationship.

OBJECTIVE: To evaluate the role of sleep in the relationship of intrusive thoughts/avoidance behaviors to natural killer cell (NKC) number and function. METHOD: Twenty-nine individuals seeking treatment for bereavement-related depression were studied in the sleep laboratory. Background and clinical variables, including the Impact of Event Scale (IES) and the Hamilton Rating Scale for Depression (HRSD), were administered during the week preceding a 3-night sleep study. Blood samples were collected upon awakening after the second or third night of sleep. RESULTS: Greater frequency of intrusive thoughts and avoidance behaviors was associated with more time spent awake during the first non-rapid eye movement period (NREM-1) and lower NKC number (p values < .01). Greater time spent awake during NREM-1 was associated with lower NKC numbers (p < .05). Regression analyses revealed that the significant relationship between symptoms of intrusion/avoidance and NKC number was no longer significant when time spent awake during NREM-1 was entered into the regression equation. Time spent awake during NREM-1 accounted for 12% of the variance in NKC number (p < .05), whereas intrusion/avoidance accounted for 7% of the variance in NKC number (NS). CONCLUSIONS: These results suggest that EEG-assessed sleep may be a significant correlate of the stress-immune relationship.

Adult↗
PubMed2005

Lipid signaling: sleep, synaptic plasticity, and neuroprotection.

Increasing evidence indicates that bioactive lipids participate in the regulation of synaptic function and dysfunction. We have demonstrated that signaling mediated by platelet-activating factor (PAF) and cyclooxygenase (COX)-2-synthesized PGE2 is involved in synaptic plasticity, memory, and neuronal protection [Clark GD, Happel LT, Zorumski CF, Bazan NG. Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 1992; 9:1211; Kato K, Clark GD, Bazan NG, Zorumski CF. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature 1994; 367:175; Izquierdo I, Fin C, Schmitz PK, et al. Memory enhancement by intrahippocampal, intraamygdala or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance. Proc Natl Acad Sci USA 1995; 92:5047; Chen C, Magee CJ, Bazan NG. Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J Neurophysiol 2002; 87:2851]. Recently, we found that prolonged continuous wakefulness (primarily rapid eye movement (REM)-sleep deprivation, SD) causes impairments in hippocampal long-term synaptic plasticity and hippocampus-dependent memory formation [McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG, Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 2003; 23:9687]. To explore the mechanisms underlying SD-induced impairments, we have studied several bioactive lipids in the hippocampus following SD. It appears that SD causes increases in prostaglandin D2 (PGD2) and 2-arachidonylglycerol (2-AG), and a decrease in PGE2, suggesting that these lipid messengers participate in memory consolidation during REM sleep. We have also explored the formation of endogenous neuroprotective lipids. Toward this aim, we have used ischemia-reperfusion damage and LC-PDA-ESI-MS-MS-based lipidomic analysis and identified docosanoids derived from synaptic phospholipid-enriched docosahexaenoic acid. Some of the docosanoids exert potent neuroprotective bioactivity [Marcheselli VL, Hong S, Lukiw WJ, et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278:43807; Mukherjee PK, Marcheselli VL, Serhan CN, Bazan, NG. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Nat Acad Sci USA 2004; 101:8491). Taken together, these observations that signaling lipids participate in synaptic plasticity, cognition, and survival indicate that lipid signaling is closely associated with several functions (e.g; learning and memory, sleep, and experimental stroke) and pathologic events. Alterations in endogenous signaling lipids or their receptors resulting from drug abuse lead to changes in synaptic circuitry and induce profound effects on these important functions. In the present article, we will briefly review bioactive lipids involved in sleep, synaptic transmission and plasticity, and neuroprotection, focusing mainly on our experimental studies and how these signaling molecules are related to functions and implicated in some neurologic disorders.

Animals↗
PubMed2004

Lack of delta waves and sleep disturbances during non-rapid eye movement sleep in mice lacking alpha1G-subunit of T-type calcium channels.

T-type calcium channels have been implicated as a pacemaker for brain rhythms during sleep but their contribution to behavioral states of sleep has been relatively uncertain. Here, we found that mice lacking alpha1(G) T-type Ca(2+) channels showed a loss of the thalamic delta (1-4 Hz) waves and a reduction of sleep spindles (7-14 Hz), whereas slow (<1 Hz) rhythms were relatively intact, when compared with the wild-type during urethane anesthesia and non-rapid eye movement (NREM) sleep. Analysis of sleep disturbances, as defined by the occurrence of brief awakening (BA) episodes during NREM sleep, revealed that mutant mice exhibited a higher incidence of BAs of >16 sec compared with the wild-type, whereas no difference was seen in BAs of <16 sec between the two genotypes. These results are consistent with the previous idea of the distinct nature of delta oscillations and sleep spindles from cortically generated slow waves. These results also suggest that the alpha1(G)-subunit of T-type calcium channels plays a critical role in the genesis of thalamocortical oscillations and contributes to the modulation of sleep states and the transition between NREM sleep and wake states.

Animals↗
PubMed1989

Alzheimer's disease. Sleep and sleep/wake patterns.

Significant changes in sleep/wake patterns, particularly loss of SWS and increased amount and frequency of nighttime wakefulness, apparently occur even at an early stage of the AD process. These disruptions of nighttime sleep increase in magnitude with increasing severity of dementia. While the REM sleep of early stage AD patients is relatively unaffected by the disease process, later stages of AD are marked by significant losses of REM sleep and perhaps more importantly the breakdown of the sleep/wake circadian rhythm with significant amounts of sleep occurring during the day. This daytime sleep is of poor quality however, consisting almost exclusively of stages 1 and 2 sleep and does not compensate for the nighttime losses of SWS and REM sleep experienced by AD patients. These findings clearly support the clinical observations and anecdotal reports of sleep disturbance in AD patients. It is of interest to note that sleep is disrupted quite early in the disease process. In our study of early stage AD patients all were community dwelling and had relatively mild cognitive impairment (average MMS scores of 22.7). Despite this, significant increases in frequency and duration of awakening from sleep and reductions of SWS were observed in these patients. These findings indicate that when a patient is suspected of having AD it may be worthwhile as part of the evaluative and diagnostic process to caution both the patient and the patient's family that they might expect to see significant changes in sleep/wake patterns even though the patient's level of day-to-day functioning may still be high. It is also important to consider warning AD patients' families that as the disease progresses they should expect to see not only a worsening of nocturnal sleep quality but a breakdown of the circadian sleep/wake rhythm and an increase in daytime napping behavior by the patient. Families need to be encouraged to try and minimize the napping behavior of the patient in an effort to consolidate sleep into the night. This may have the effect of somewhat attenuating the amount of nocturnal disruption of sleep that accompanies progression of the disease.

Aged↗
PubMed2002

Factors related to the occurrence of isolated sleep paralysis elicited during a multi-phasic sleep-wake schedule.

STUDY OBJECTIVES: To further investigate mechanisms of isolated sleep paralysis (ISP) in normal individuals, we experimentally elicited ISPs by facilitating sleep onset REM periods (SOREMP), a prerequisite of ISPs, and examined behavioral and psychological measurements relating to ISP appearances. DESIGN: The multi-phasic sleep/wake schedule (MPS) began at approximately midnight and ended when net sleep reached 7.5 hours. Participants were awakened after every 5 min of REM sleep to obtain a maximum number of SOREMPs. Upon each awakening, mentation reports and subjective measurements were collected. Performance tests were then assigned. SETTING: Sleep lab, Tokyo Metropolitan Institute for Neurosciences, Japan. PARTICIPANTS: Thirteen healthy Japanese students (10 males) with high self-reported frequencies of ISPs but no other narcolepsy-related symptoms. INTERVENTIONS MEASUREMENTS AND RESULTS: From 184 sleep interruptions, 8 ISP episodes were obtained. In within participant comparisons between episodes with and without ISPs, the vigilance task (VT) reaction times were elevated before SOREMPs with ISPs. In between analyses (ISP vs non-ISP), the ISP group showed poorer performance, more complaints of physical, mental, and neurotic symptoms, increased subjective fatigue and increased stage 1 throughout the entire schedule. VT hit rates remained constant in the non-ISP group, but dropped in the later part of schedule in the ISP group. Subjective sleepiness dropped over time in the non-ISP group while it slightly increased in the ISP group. CONCLUSIONS: ISP is likely to appear as a phenotype of REM dissociation during SOREMP when participants with low tolerance for disrupted sleep-wake rhythms are placed in this type of schedule.

Adult↗
PubMed2002

Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice.

Recent studies demonstrated that mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show age-independent and age-related deficits in spatial learning. We used behavioral and electrophysiological techniques to determine in young and aged PDAPP mice whether deficits in spatial learning also involve alterations in sleep-wake states, thermoregulation and motor activity. Consistent with earlier studies, young PDAPP mice exhibited selective age-independent deficits using spatial, but not random and serial strategies in the circular maze. Aged PDAPP mice exhibited deficits using all search strategies. The core body temperature (Tb) in young and aged PDAPP mice was significantly lower than in age-matched non-transgenic (non-Tg) littermates. During the dark period, the motor activity (LMA) was significantly increased in young PDAPP mice, but not in aged PDAPP mice. During the light period, young PDAPP mice showed a reduction in the generation of rapid-eye-movement (REM) sleep. In contrast, aged PDAPP mice exhibited a reduction in the amount of time spent in W and an increase in SWS during the light period. Aged PDAPP mice also showed an increase in the amount of time spent in W and a reduction in REM sleep during the dark period. Our findings support previous reports indicating deficits in spatial learning in young and aged PDAPP mice. These data also suggest that PDAPP mice exhibit age-independent and age-related deficits in neural mechanisms regulating visuospatial learning, the total amount and the circadian distribution of sleep-wake states, thermoregulation and motor activity.

Aging↗
PubMed2004

The sleep-promoting action of ramelteon (TAK-375) in freely moving cats.

INTRODUCTION: Ramelteon (TAK-375) is an MT1/MT2 receptor agonist being studied for the treatment of insomnia and circadian rhythm sleep disorders. We compared the behavioral effects of ramelteon and exogenous melatonin in freely moving cats. METHODS: Ramelteon and melatonin were each suspended in a 0.5% (weight per volume) methylcellulose solution and administered orally to freely moving cats. In the control trial, each cat was given vehicle. Each dose of ramelteon or melatonin was compared with the vehicle control in a crossover design. Electroencephalogram, electromyogram, and electrooculogram recordings were assessed. RESULTS: Ramelteon significantly decreased wakefulness at doses of 0.001,0.01, and 0.1 mg/kg, increased slow-wave sleep at doses of 0.001, 0.01, and 0.1 mg/kg, and increased rapid eye movement sleep at a dose of 0.1 mg/kg, compared with the vehicle controls, as assessed by analysis of variance. The effects of ramelteon lasted for up to 6 hours when evaluated by reduction of wakefulness. Exogenous melatonin (0.01-1 mg/kg) significantly increased slow-wave sleep, but the effect was weaker than that of ramelteon and lasted for only 2 hours. The lowest doses of ramelteon (0.0001 mg/kg) and melatonin (0.001 mg/kg) had no significant effect on sleep-wakefulness stage. CONCLUSIONS: Ramelteon was more effective than exogenous melatonin in promoting and maintaining sleep in freely moving cats. Based on its unique mechanism of action, ramelteon should be studied further to evaluate its potential for the treatment of sleep disorders.

Animals↗
PubMedDate not supplied

Central cholinergic challenging of migraine by testing second-generation anticholinesterase drugs.

The antinociceptive activity of donepezil, a novel cholinesterase inhibitor, was investigated in the mouse hot plate test. Donepezil (5 to 10 mg kg(-1) i.p.) induced a dose-dependent antinociception that reached its maximum effect 15 minutes after injection. Donepezil antinociception was prevented by the antimuscarinic drug scopolamine. At analgesic doses, donepezil did not alter gross animal behavior. These results indicate that donepezil is endowed by muscarinic antinociceptive properties, suggesting this compound as a potential therapeutic approach for the treatment of painful pathologies. Therefore, we investigated donepezil's effect in migraine. Donepezil (5 mg per os, evening assumption) was effective as a prophylatic agent in patients suffering from migraine with or without aura by reducing the number of hours with pain, the number of attacks, and the severity of the pain attack. The efficacy of donepezil was compared with that of the beta-blocker propranolol (40 mg bid per os), showing higher activity. Response rates of a large-sized open study devoid of entry criteria regarding migraine subtypes suggest the drug as an excellent prophylactic compound for migraine in general practice. Clinical results also indicate that the activation of the cholinergic system can represent a novel prophylactic approach to migraine.

Adrenergic beta-Antagonists↗
PubMed2003

Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats.

Narcolepsy, a disabling neurological disorder characterized by excessive daytime sleepiness, sleep attacks, sleep fragmentation, cataplexy, sleep-onset rapid eye movement sleep periods and hypnagogic hallucinations was recently linked to a loss of neurons containing the neuropeptide hypocretin. There is considerable variability in the severity of symptoms between narcoleptic patients, which could be related to the extent of neuronal loss in the lateral hypothalamus. To investigate this possibility, we administered two concentrations (90 ng or 490 ng in a volume of 0.5 microl) of the neurotoxin hypocretin-2-saporin, unconjugated saporin or saline directly to the lateral hypothalamus and monitored sleep, the entrained and free-running rhythm of core body temperature and activity. Neurons stained for hypocretin or for the neuronal specific marker were counted in the perifornical area, dorsomedial and ventromedial nucleus of the hypothalamus. More neuronal nuclei (NeuN) cells were destroyed by the higher concentration of hypocretin-2-saporin (-55%) compared with the lower concentration (-34%) in the perifornical area, although both concentrations lesioned the hypocretin neurons almost equally well (high concentration=91%; low concentration=88%). The high concentration of hypocretin-2-saporin also lesioned neurons in the dorsomedial nucleus of the hypothalamus and ventromedial nucleus of the hypothalamus. Narcoleptic-like sleep behavior was produced by both concentrations of the hypocretin-2-saporin. The high concentration produced a larger increase in non-rapid eye movement sleep amounts during the normally active night cycle than low concentration. Neither concentration of hypocretin-2-saporin disrupted the phase or period of the core temperature or activity rhythms. The low concentration of unconjugated saporin did not significantly lesion hypocretin or neurons and did not alter sleep. The high concentration of unconjugated saporin produced some loss of neuronal nuclei-immunoreactive (NeuN-ir) neurons and hypocretin immunoreactive neurons, but only a transient increase in non-rapid eye movement sleep. These results led us to conclude that the extent of hypocretin neuronal loss together with an accompanying loss of cells in the lateral hypothalamus may explain the differences in severity of symptoms seen in human narcolepsy.

Animals↗
PubMed2005

Injection of glutamate into the pedunculopontine tegmental nuclei of anesthetized rat causes respiratory dysrhythmia and alters EEG and EMG power.

The pedunculopontine tegmental nucleus (PPT) has been shown to have important functions relevant to the regulation of behavioral states and various motor control systems, including breathing control. Our previous work has shown that the activation of neurons within the PPT, a structure that is typically active during rapid eye movement (REM) sleep, can produce respiratory disturbances in freely moving and anesthetized rats. The aim of this study was to test the hypothesis that respiratory modulation by the PPT in anesthetized rats can be evoked in the absence of other signs of an REM-sleep-like state. We characterized electroencephalogram (EEG) and electromyogram (EMG) changes during respiratory disturbances induced by glutamatergic stimulation of the PPT in spontaneously breathing, adult male Sprague-Dawley rats anesthetized with a ketamine/xylazine combination or with nembutal. Respiratory movements were monitored by a piezoelectric strain gauge. Two-barrel glass pipettes were used to pressure inject glutamate, to probe for respiratory effective sites within the PPT, and to inject oil red dye at the end of the experiments for histological verification of the injection sites. The EEGs were recorded from the sensorimotor cortex, hippocampus, and from the pons contralateral from the injection site. The EMGs were recorded from the genioglossus muscle. The initial response to glutamate injection into the respiratory modulating region of the PPT was always a respiratory pattern disturbance. Subsequent activation of EMG and EEG often occurred in ketamine/xylazine-anesthetized rats, but REM-sleep-like patterns were not observed. Respiratory pattern and EMG power changes in nembutal-anesthetized rats were similar, but EEG activation was never observed. Thus, we conclude that respiratory suppression produced by the local activation of PPT neurons may not necessarily be accompanied by an REM-sleep-like cortical state in this anesthetized model.

Anesthesia↗
PubMed1976

Fugue states in sleep and wakefulness: a psychophysiological study.

A patient's refusal to participate in recommended treatment is a problem faced in all branches of medicine. However, psychiatry faces special problems because of its authority to impose hospitalization and treatment on unwilling patients. Nowhere is this more poignant than in the treatment of patients exhibiting suicidal behavior where the potential for imminent self-destruction exists. As part of a prospective study to develop utilization review standards for the hospitalization of suicide attempters, cases were identified where there was independent agreement between both the experts' standards and the treating resident psychiatrists that hospitalization was required. Despite this agreement, the patients were not hospitalized because the patients refused. By most criteria, these patients were a high risk group. They had made repeated suicide attempts, used lethal means which eventuated in serious medical consequences, and were still suicidal when referred for treatment. The emergency room psychiatrists reported feeling confused, anxious, and annoyed in dealing with these patients, and the patients signed out against medical advice. A review of these cases indicates that discussions of social control vs. medical responsibility and clear criteria for hospitalization should be incorporated into residency training programs since the emergency room resident faces these tension-producing issues frequently with several different types of patients. Moreover, utilization review criteria may help to set standards which will assist the psychiatrist in making these difficult decisions.

Dissociative Disorders↗