A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats

Anesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of b...

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Main Authors: Rachel Ward-Flanagan, Alto S. Lo, Elizabeth A. Clement, Clayton T. Dickson
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/7/3608
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author Rachel Ward-Flanagan
Alto S. Lo
Elizabeth A. Clement
Clayton T. Dickson
author_facet Rachel Ward-Flanagan
Alto S. Lo
Elizabeth A. Clement
Clayton T. Dickson
author_sort Rachel Ward-Flanagan
collection DOAJ
description Anesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of brain states, and consequently have differential effects on a multitude of neurophysiological factors, these outcomes vary based on dosages, the animal species used, and the pharmacological mechanisms specific to each anesthetic agent. Thus, our aim was to conduct a controlled comparison of spontaneous electrophysiological dynamics at a surgical plane of anesthesia under six common research anesthetics using a ubiquitous animal model, the Sprague-Dawley rat. From this direct comparison, we also evaluated which anesthetic agents may serve as pharmacological proxies for the electrophysiological features and dynamics of unconscious states such as sleep and coma. We found that at a surgical plane, pentobarbital, isoflurane and propofol all produced a continuous pattern of burst-suppression activity, which is a neurophysiological state characteristically observed during coma. In contrast, ketamine-xylazine produced synchronized, slow-oscillatory activity, similar to that observed during slow-wave sleep. Notably, both urethane and chloral hydrate produced the spontaneous, cyclical alternations between forebrain activation (REM-like) and deactivation (non-REM-like) that are similar to those observed during natural sleep. Thus, choice of anesthesia, in conjunction with continuous brain state monitoring, are critical considerations in order to avoid brain-state confounds when conducting neurophysiological experiments.
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spelling doaj.art-1b530125c4b84178b1335ccd236654f32023-11-30T23:19:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237360810.3390/ijms23073608A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley RatsRachel Ward-Flanagan0Alto S. Lo1Elizabeth A. Clement2Clayton T. Dickson3Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, CanadaDepartment of Psychology, University of Alberta, Edmonton, AB T6G 2R3, CanadaNeuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, CanadaNeuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, CanadaAnesthesia is a powerful tool in neuroscientific research, especially in sleep research where it has the experimental advantage of allowing surgical interventions that are ethically problematic in natural sleep. Yet, while it is well documented that different anesthetic agents produce a variety of brain states, and consequently have differential effects on a multitude of neurophysiological factors, these outcomes vary based on dosages, the animal species used, and the pharmacological mechanisms specific to each anesthetic agent. Thus, our aim was to conduct a controlled comparison of spontaneous electrophysiological dynamics at a surgical plane of anesthesia under six common research anesthetics using a ubiquitous animal model, the Sprague-Dawley rat. From this direct comparison, we also evaluated which anesthetic agents may serve as pharmacological proxies for the electrophysiological features and dynamics of unconscious states such as sleep and coma. We found that at a surgical plane, pentobarbital, isoflurane and propofol all produced a continuous pattern of burst-suppression activity, which is a neurophysiological state characteristically observed during coma. In contrast, ketamine-xylazine produced synchronized, slow-oscillatory activity, similar to that observed during slow-wave sleep. Notably, both urethane and chloral hydrate produced the spontaneous, cyclical alternations between forebrain activation (REM-like) and deactivation (non-REM-like) that are similar to those observed during natural sleep. Thus, choice of anesthesia, in conjunction with continuous brain state monitoring, are critical considerations in order to avoid brain-state confounds when conducting neurophysiological experiments.https://www.mdpi.com/1422-0067/23/7/3608urethanechloral hydrateketamine-xylazinepentobarbitalpropofolisoflurane
spellingShingle Rachel Ward-Flanagan
Alto S. Lo
Elizabeth A. Clement
Clayton T. Dickson
A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
International Journal of Molecular Sciences
urethane
chloral hydrate
ketamine-xylazine
pentobarbital
propofol
isoflurane
title A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
title_full A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
title_fullStr A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
title_full_unstemmed A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
title_short A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
title_sort comparison of brain state dynamics across common anesthetic agents in male sprague dawley rats
topic urethane
chloral hydrate
ketamine-xylazine
pentobarbital
propofol
isoflurane
url https://www.mdpi.com/1422-0067/23/7/3608
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