Short-term Memory Impairment after Isoflurane in Mice Is Prevented by the α5 γ-Aminobutyric Acid Type A Receptor Inverse Agonist L-655,708

Author:

Saab Bechara J.1,MacLean Ashley J. B.2,Kanisek Marijana3,Zurek Agnieszka A.4,Martin Loren J.5,Roder John C.6,Orser Beverley A.7

Affiliation:

1. Graduate Student, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, Department of Molecular Genetics, University of Toronto, Toronto, Canada.

2. Undergraduate Student, Department of Pharmacology and Toxicology, University of Toronto.

3. Technician, Samuel Lunenfeld Research Institute, Mount Sinai Hospital.

4. Graduate Student, Department of Physiology, University of Toronto.

5. Graduate Student, Institute of Medical Science, University of Toronto.

6. Senior Investigator, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Professor, Departments of Molecular Genetics and Physiology, University of Toronto.

7. Professor, Departments of Anesthesia and Physiology, University of Toronto, Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Abstract

Background Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. Inhibitory α5 subunit-containing γ-aminobutyric acid subtype A receptors (α5GABAA) are known to play a critical role in memory processes and are highly sensitive to positive modulation by anesthetics. We postulated that inhibiting the activity of α5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period. Methods Mice were pretreated with L-655,708, an α5GABAA receptor-selective inverse agonist, or vehicle. They were then exposed to isoflurane for 1 h (1.3%, or 1 minimum alveolar concentration, or air-oxygen control). Then, either 1 or 24 h later, mice were conditioned in fear-associated contextual and cued learning paradigms. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 min, 1 h, and 24 h after isoflurane were also examined. Results Motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 h. The α5GABAA receptor inverse agonist, L-655,708, completely prevented memory deficits without changing the immobilizing dose of isoflurane. Trace concentrations of isoflurane were measured in the brain 24 h after treatment. Conclusions Memory deficits occurred long after the sedative, analgesic, and anxiolytic effects of isoflurane subsided. L-655,708 prevented memory deficit, suggesting that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference50 articles.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.7亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2025 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3