A Neurochemical Perspective on States of Consciousness

Watson, Christopher J.; Baghdoyan, Helen A.; Lydic, Ralph

doi:10.1007/978-1-60761-462-3_3

Cited by 5 publications

(7 citation statements)

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“…There is a convergence of evidence that sleep neurobiology can help elucidate some of the mechanisms by which anesthetics cause a loss of wakefulness (reviewed in37–41). Therefore, the goal of experiment 1 was to phenotype states of sleep and wakefulness as a prelude to future studies designed to characterize responses of HCR and LCR rats to intravenous and volatile anesthetics.…”

Section: Methodsmentioning

confidence: 99%

Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy Are Distinct Phenotypes in a Rat Model of Metabolic Syndrome

Muncey

Saulles²,

Koch

et al. 2010

Anesthesiology

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Background Sleep apnea, hypertension, atherosclerosis, and obesity are features of metabolic syndrome associated with decreased restorative sleep and increased pain. These traits are relevant for anesthesiology because they confer increased risks of a negative anesthetic outcome. This study tested the one-tailed hypothesis that rats bred for low intrinsic aerobic capacity have enhanced nociception and disordered sleep. Methods Rats were from a breeding strategy that selected for low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). Four different phenotypes were quantified. Rats (n=12) underwent von Frey sensory testing, thermal nociceptive testing (n=12), electrographic recordings of sleep and wakefulness (n=16), and thermal nociceptive testing before and for six weeks after a unilateral chronic neuropathy of the sciatic nerve (n=14). Results Paw withdrawal latency to a thermal nociceptive stimulus was significantly (P<0.01) less in LCR than HCR rats. There were significant differences in sleep. LCR rats spent significantly (P<0.01) more time awake (18%) and less time in non-rapid eye movement sleep (−19%) than HCR rats. Non-rapid eye movement sleep episodes were of shorter duration (−34%) in LCR than HCR rats. Rapid eye movement sleep of LCR rats was significantly more fragmented than Rapid eye movement sleep of HCR rats. LCR rats required two weeks longer than HCR rats to recover from peripheral neuropathy. Conclusions Rodents with low aerobic capacity exhibit features homologous to human metabolic syndrome. This rodent model offers a novel tool for characterizing the mechanisms through which low aerobic function and obesity might confer increased risks for anesthesia.

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Section: Methodsmentioning

confidence: 99%

Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy Are Distinct Phenotypes in a Rat Model of Metabolic Syndrome

Muncey

Saulles²,

Koch

et al. 2010

Anesthesiology

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“…The EEG patterns during recovery from coma — coma, vegetative state, and minimally conscious state — resemble the patterns during general anesthesia, sleep, and the awake state. EEG tracings during sleep are from Watson et al 5 …”

Section: Figurementioning

confidence: 99%

General Anesthesia, Sleep, and Coma

2010

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In the united states, nearly 60,000 patients per day receive general anesthesia for surgery. 1 General anesthesia is a drug-induced, reversible condition that includes specific behavioral and physiological traits -unconsciousness, amnesia, analgesia, and akinesia -with concomitant stability of the autonomic, cardiovascular, respiratory, and thermoregulatory systems. 2 General anesthesia produces distinct patterns on the electroencephalogram (EEG), the most common of which is a progressive increase in low-frequency, high-amplitude activity as the level of general anesthesia deepens 3,4 (Fig. 1). How anesthetic drugs induce and maintain the behavioral states of general anesthesia is an important question in medicine and neuroscience. 6 Substantial insights can be gained by considering the relationship of general anesthesia to sleep and to coma.Humans spend approximately one third of their lives asleep. Sleep, a state of decreased arousal that is actively generated by nuclei in the hypothalamus, brain stem, and basal forebrain, is crucial for the maintenance of health. 7,8 Normal human sleep cycles between two states -rapid-eye-movement (REM) sleep and non-REM sleep -at approximately 90-minute intervals. REM sleep is characterized by rapid eye movements, dreaming, irregularities of respiration and heart rate, penile and clitoral erection, and airway and skeletal-muscle hypotonia. 7 In REM sleep, the EEG shows active high-frequency, lowamplitude rhythms (Fig. 1). Non-REM sleep has three distinct EEG stages, with higheramplitude, lower-frequency rhythms accompanied by waxing and waning muscle tone, decreased body temperature, and decreased heart rate.Coma is a state of profound unresponsiveness, usually the result of a severe brain injury. 9 Comatose patients typically lie with eyes closed and cannot be roused to respond appropriately to vigorous stimulation. A comatose patient may grimace, move limbs, and have stereotypical withdrawal responses to painful stimuli yet make no localizing responses or discrete defensive movements. As the coma deepens, the patient's responsiveness even to painful stimuli may diminish or disappear. Although the patterns of EEG activity observed in comatose patients depend on the extent of the brain injury, they frequently resemble the high-amplitude, low-frequency activity seen in patients under general anesthesia 10 (Fig. 1). General anesthesia is, in fact, a reversible drug-induced coma. Nevertheless, anesthesiologists refer to it as "sleep" to avoid disquieting patients. Unfortunately, anesthesiologists also use the word "sleep" in technical descriptions to refer to Copyright © 2010 CLINICAL SIGNS AND EEG PAT TERNS OF UNCONSCIOUSNESS INDUCED BY GENER AL ANESTHESIAThe clinical signs and EEG patterns of general anesthesia-induced unconsciousness can be described in relation to the three periods in which they appear: induction, maintenance, and emergence. INDUCTION PERIODBefore induction, the patient has a normal, active EEG, with prominent alpha activity (10 Hz) when the eyes are clo...

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“…Abbreviations: XII – hypoglossal nucleus; BF – basal forebrain; DRN – dorsal raphé nucleus; LC – locus coeruleus; LDT – laterodorsal tegmental nucleus; LH – lateral hypothalamus; MPO – medial preoptic area; PFC – prefrontal cortex; PPT – pedunculopontine tegmental nucleus; PnC – pontine reticular formation, caudal part; PnO – pontine reticular formation, oral part; TMN – tuberomamillary nucleus; TNC – trigeminal nucleus complex; VLPO – ventrolateral preoptic area; VTA – ventral tegmental area; 5HT – serotonin; ACh – acetylcholine; Ado – adenosine; Asp – aspartate; DA – dopamine; GABA – γ-aminobutyric acid; Glu – glutamate; Gly – glycine; His – histamine; Hcrt – hypocretin; NE – norepinephrine; NO – nitric oxide; Noc – nociceptin; Ser – serine; 5HT – serotonin; Tau – taurine. Figure reprinted from Watson et al, 20101 with permission.…”

Section: Figuresmentioning

confidence: 99%

“…This chapter and Figure 1 provide an overview of neurotransmitters and brain regions currently known to modulate states of sleep and wakefulness. This overview of sleep neuropharmacology can be read as a précis of a recent chapter1 and interested readers are referred elsewhere for detailed reviews on sleep 2–8…”

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confidence: 99%

Neuropharmacology of Sleep and Wakefulness

Watson

Baghdoyan

Lydic

2010

Sleep Medicine Clinics

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Synopsis The development of sedative/hypnotic molecules has been empiric rather than rational. The empiric approach has produced clinically useful drugs but for no drug is the mechanism of action completely understood. All available sedative/hypnotic medications have unwanted side effects and none of these medications creates a sleep architecture that is identical to the architecture of naturally occurring sleep. This chapter reviews recent advances in research aiming to elucidate the neurochemical mechanisms regulating sleep and wakefulness. One promise of rational drug design is that understanding the mechanisms of sedative/hypnotic action will significantly enhance drug safety and efficacy.

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A Neurochemical Perspective on States of Consciousness

Cited by 5 publications

References 352 publications

Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy Are Distinct Phenotypes in a Rat Model of Metabolic Syndrome

Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy Are Distinct Phenotypes in a Rat Model of Metabolic Syndrome

General Anesthesia, Sleep, and Coma

Neuropharmacology of Sleep and Wakefulness

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