在社交大鼠中使用套式遥测技术同时评估中枢神经和呼吸系统:“3Rs”原理在核心电池安全药理学研究中的应用

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Raafat Fares, Pascal Champéroux
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引用次数: 0

摘要

中枢神经系统(CNS)和呼吸系统在安全药理学核心组研究中进行常规研究。对于小分子,在两项不同的研究中,经常对大鼠的两个重要器官系统进行评估。随着大鼠夹套外部遥测小型化技术(DECRO系统)的出现,在一项研究中同时评估改良的欧文或功能观察电池(FOB)测试和呼吸(Resp)研究已成为可能。因此,本研究的目的是在配有护套遥测的成对饲养的大鼠中同时进行FOB和Resp研究,并评估对照组、巴氯芬、咖啡因和可乐定治疗组(即三种药物同时具有呼吸和中枢神经系统作用)中这种组合的可行性和结果。我们的结果提供了证据,证明在同一只大鼠中同时进行Resp和FOB评估是可行的,结果是成功的。3种参考化合物的预期中枢神经系统和呼吸系统影响在每次测定中都被准确捕获,证实了结果的相关性。此外,心率和活动水平被记录为额外的参数,使该设计成为大鼠非临床安全评估的增强方法。这项工作提供了明确的证据,证明“3Rs”原则可以有效地应用于核心电池安全药理学研究,同时符合全球监管指南。该模型证明了动物使用的减少和程序的改进。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Simultaneous assessment of central nervous and respiratory systems using jacketed telemetry in socially-housed rats: Application of the “3Rs” principles in core battery safety pharmacology studies

Central nervous (CNS) and respiratory systems are routinely investigated in safety pharmacology core battery studies. For small molecules, the assessment of both vital organ systems is frequently done in rats in two distinct studies. With the advent of a miniaturized technology of jacketed external telemetry for rats (DECRO system), the simultaneous assessment of modified Irwin's or functional observational battery (FOB) test and respiratory (Resp) studies has become possible within a single study. Therefore, the objectives of this study were to perform the FOB and the Resp studies simultaneously in pair-housed rats fitted with jacketed telemetry, and to assess the feasibility and the outcome of this combination in control, baclofen, caffeine, and clonidine treated groups, i.e., with three agents having both respiratory and CNS effects. Our results provided evidence that performing both Resp and FOB assessment simultaneously in the same rat was feasible and the outcome was successful. The expected CNS and respiratory effects of the 3 reference compounds were accurately captured in each assay confirming the results' relevance. In addition, heart rate and activity level were recorded as additional parameters making this design as an enhanced approach for nonclinical safety assessment in rats. This work provides clear evidence that the “3Rs” principles can be effectively applied in core battery safety pharmacology studies while remaining in compliance with worldwide regulatory guidelines. Both reduction in animal use and refinements in procedures are demonstrated with this model.

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来源期刊
Journal of pharmacological and toxicological methods
Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY
CiteScore
3.60
自引率
10.50%
发文量
56
审稿时长
26 days
期刊介绍: Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.
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