Dopaminergic psychostimulants cause arousal from isoflurane-induced sedation without reversing memory impairment in rats.

amnesia arousal dopamine isoflurane memory psychostimulant

Journal

British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541

Informations de publication

Date de publication:
03 Jul 2024
Historique:
received: 15 03 2024
revised: 30 04 2024
accepted: 04 05 2024
medline: 5 7 2024
pubmed: 5 7 2024
entrez: 4 7 2024
Statut: aheadofprint

Résumé

Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory. Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated. Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane. Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.

Sections du résumé

BACKGROUND BACKGROUND
Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory.
METHODS METHODS
Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated.
RESULTS RESULTS
Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane.
CONCLUSIONS CONCLUSIONS
Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.

Identifiants

DOI: 10.1016/j.bja.2024.05.026 PMID: 38965013
pubmed: 38965013
pii: S0007-0912(24)00336-2
doi: 10.1016/j.bja.2024.05.026
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Auteurs

Michael R Fettiplace (MR)

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA. Electronic address: fettiplace@gmail.com.

Kathleen F Vincent (KF)

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.

Angel Cho (A)

Touro College of Osteopathic Medicine, New York, NY, USA.

Emmaline Dillon (E)

Department of Cell Biology and Physiology, Brigham Young University, Provo, UT, USA.

Brendan M Stapley (BM)

Department of Cell Biology and Physiology, Brigham Young University, Provo, UT, USA.

Victoria Stewart (V)

University of California Irvine School of Medicine, Irvine, CA, USA.

Ken Solt (K)

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.

Classifications MeSH