Central cholinergic depletion induced by 192 IgG-Saporin alleviates the sedative effects of propofol in rats

Pain, Laure; Jeltsch, Hélène; Lehmann, Olivia; Lazarus, Christine; Laalou, Fatem-Zohra; Cassel, Jean‐Christophe

doi:10.1093/bja/85.6.869

Cited by 30 publications

(9 citation statements)

References 25 publications

(8 reference statements)

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“…An anticholinesterase that increased central Ach levels was shown to reduce the depth of anesthesia induced by propofol or isoflurane (Meuret et al, 2000;Hudetz et al, 2003). Pain et al (2000) reported that central Ach depletion by intracerebroventricular (icv) administration of 192IgG-saporin reduced the sedative potency of low-dose (30 mg/kg i.p.) propofol, although a subsequent study (Laalou et al, 2008) reported that the same depletion increased the anesthesia potency of propofol (N100 mg/kg i.p.).…”

Section: Introductionmentioning

confidence: 99%

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Leung

Petropoulos

Shen

et al. 2011

Experimental Neurology

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"Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics" (2011). Physiology and Pharmacology Publications. 72. https://ir.lib.uwo.ca/physpharmpub/72 This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long-Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and ChAT-positive neurons in the medial septum-vertical limb of the diagonal band were not different between lesioned and control rats. When a general anesthetic was administered, lesioned compared to control rats showed significantly longer duration of loss of righting reflex (LORR) after propofol (5 or 10 mg/kg i.v.), pentobarbital (20 or 40 mg/kg i.p.) but not halothane (2%). However, the behavioral excitation, as indicated by horizontal movements, induced by halothane was reduced in lesioned as compared to control rats. Reversible inactivation of NBM with GABA A receptor agonist muscimol increased slow waves in the neocortex during awake immobility, and prolonged the duration of LORR and loss of tail-pinch response after propofol, pentobarbital and halothane. In summary, lesion of NBM cholinergic neurons or inactivation of the NBM prolonged the LORR response to general anesthetic drugs.

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Section: Introductionmentioning

confidence: 99%

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Leung

Petropoulos

Shen

et al. 2011

Experimental Neurology

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“…For example, the immunotoxin 192 IgG-Saporin selectively destroys basal forebrain cholinergic neurons. In rat, intracerebroventricular administration of 192 IgG-Saporin caused a reduction in ACh levels in frontoparietal cortex and hippocampus and a decrease in propofol-induced locomotor inhibition 16 . These findings suggest that inhibition of basal forebrain cholinergic neurons contributes to the hypnotic effect of propofol 16 .…”

Section: 4mentioning

confidence: 94%

Neurochemical Modulators of Sleep and Anesthetic States

Dort

Baghdoyan

Lydic

2008

International Anesthesiology Clinics

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The regulation of consciousness is a fundamental question that has a long and storied association with philosophy. Today, consciousness studies command a central position in contemporary neuroscience 1-3. The complexities of consciousness studies and the pressing demands of clinical care have led most anesthesiologists to focus on research problems with pragmatic outcomes. Yet the ability to accurately assess and manipulate states of consciousness with anesthetic drugs is the ultimate concern for every surgical patient and anesthesia provider. This volume recognizes consciousness studies as a legitimate and accessible concern for anesthesiology. This chapter considers the relationship between molecules known to regulate the loss of consciousness during anesthesia and molecules that regulate the loss of consciousness during physiological sleep. Sleep neurobiology has been shown to provide unique insights into the study of consciousness 4-6. The proposal 7,8 that neuronal networks that evolved to generate states of sleep and wakefulness also contribute to the generation of anesthetic states has been supported by many laboratories 9-19. There is evidence that the loss of consciousness during sleep is caused, in part, by the loss of functional connectivity and information processing 20. Functional connectivity is critically dependent on neurochemical transmission. Therefore, this chapter focuses on intravenous and volatile anesthetics that have been shown to alter endogenous neurotransmitters known to regulate states of consciousness. Reviews on sleep from an anesthesiology perspective are available elsewhere 8,21-24. The present overview is derived from a September 2007 PubMed title search of peer-reviewed papers linking 10 commonly used anesthetics with 11 endogenous molecules known to regulate states of consciousness. The list of intravenous anesthetics includes propofol, pentobarbital, ketamine, etomidate, and midazolam. The list of volatile anesthetics includes isoflurane, sevoflurane, nitrous oxide, xenon, and desflurane. The 11 endogenous molecules known to regulate sleep/wake states 25 include acetylcholine (ACh), gamma-aminobutyric acid (GABA), glutamate, adenosine, dopamine, histamine, serotonin, norepinephrine, hypocretin/orexin, glycine, and galanin. This 10 by 11 matrix was searched from 1950 to 2007 and identified 660 references. A search of the last 10 years (1997 to 2007) revealed a total of 192 references (Tables 1 and 2). I. Intravenous Anesthetics Alter Neurotransmitters that Regulate Sleep and Wakefulness The endogenous neurotransmitters and neuromodulators ACh, GABA, glutamate, the monoamines (dopamine, histamine, serotonin, and norepinephrine), and adenosine contribute to generating and maintaining states of sleep and wakefulness. The following section

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“…62 The small dose of adenosine A 1 agonist injected into the pontine reticular formation caused a surprisingly long duration antinociceptive effect. 377 In humans, systemic administration of sedative hypnotics that enhance the actions of GABA increase NREM sleep and decrease REM sleep. 359 Adenosine A 1 receptors are coupled to G proteins, which amplify synaptic signaling in the time domain.…”

Section: Arousal States Are Regulated By Multiple Neurotransmitters Amentioning

confidence: 99%

Sleep, Anesthesiology, and the Neurobiology of Arousal State Control

Lydic

Baghdoyan

2005

Anesthesiology

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Sleep, like breathing, is a biologic rhythm that is actively generated by the brain. Neuronal networks that have evolved to regulate naturally occurring sleep preferentially modulate traits that define states of sedation and anesthesia. Sleep is temporally organized into distinct stages that are characterized by a unique constellation of physiologic and behavioral traits. Sleep and anesthetic susceptibility are genetically modulated, heritable phenotypes. This review considers 40 yr of research regarding the cellular and molecular mechanisms contributing to arousal state control. Clinical and preclinical data have debunked and supplanted the primitive view that sleep need is a weakness. Sleep deprivation and restriction diminish vigilance, alter neuroendocrine control, and negatively impact immune function. There is overwhelming support for the view that decrements in vigilance can negatively impact performance. Advances in neuroscience provide a foundation for the sea change in public and legal perspectives that now regard a sleepdeprived individual as impaired.

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Central cholinergic depletion induced by 192 IgG-Saporin alleviates the sedative effects of propofol in rats

Cited by 30 publications

References 25 publications

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Neurochemical Modulators of Sleep and Anesthetic States

Sleep, Anesthesiology, and the Neurobiology of Arousal State Control

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