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苯环利定诱导的大鼠运动和社交行为改变的时间分离:一种自动化笼内监测系统的应用 - 对 3R 原则和临床前药物发现的意义。

Temporal dissociation of phencyclidine: Induced locomotor and social alterations in rats using an automated homecage monitoring system - implications for the 3Rs and preclinical drug discovery.

机构信息

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

School of Informatics, University of Edinburgh, Edinburgh, UK.

出版信息

J Psychopharmacol. 2020 Jul;34(7):709-715. doi: 10.1177/0269881120920455. Epub 2020 May 21.

DOI:10.1177/0269881120920455
PMID:32438848
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7675779/
Abstract

BACKGROUND

Rodent behavioural assays are widely used to delineate the mechanisms of psychiatric disorders and predict the efficacy of drug candidates. Conventional behavioural paradigms are restricted to short time windows and involve transferring animals from the homecage to unfamiliar apparatus which induces stress. Additionally, factors including environmental perturbations, handling and the presence of an experimenter can impact behaviour and confound data interpretation. To improve welfare and reproducibility these issues must be resolved. Automated homecage monitoring offers a more ethologically relevant approach with reduced experimenter bias.

AIM

To evaluate the effectiveness of an automated homecage system at detecting locomotor and social alterations induced by phencyclidine (PCP) in group-housed rats. PCP is an N-methyl-D-aspartate (NMDA) receptor antagonist commonly utilised to model aspects of schizophrenia.

METHODS

Rats housed in groups of three were implanted with radio frequency identification (RFID) tags. Each homecage was placed over a RFID reader baseplate for the automated monitoring of the social and locomotor activity of each individual rat. For all rats, we acquired homecage data for 24 h following administration of both saline and PCP (2.5 mg/kg).

RESULTS

PCP resulted in significantly increased distance travelled from 15 to 60 min post injection. Furthermore, PCP significantly enhanced time spent isolated from cage mates and this asociality occured from 60 to 105 min post treatment.

CONCLUSIONS

Unlike conventional assays, in-cage monitoring captures the temporal duration of drug effects on multiple behaviours in the same group of animals. This approach could benefit psychiatric preclinical drug discovery through improved welfare and increased between-laboratory replicability.

摘要

背景

啮齿动物行为学测定广泛用于阐明精神疾病的发病机制,并预测候选药物的疗效。传统的行为学方法仅限于短时间窗口,且需要将动物从饲养笼转移到陌生的设备中,这会引起应激。此外,包括环境干扰、操作和实验者的存在在内的各种因素都会影响行为,并使数据解释复杂化。为了提高动物福利和重现性,必须解决这些问题。自动化饲养笼监测提供了一种更具生态相关性的方法,减少了实验者的偏见。

目的

评估自动化饲养笼系统在检测群居大鼠中苯环利定(PCP)诱导的运动和社交行为改变的有效性。PCP 是一种 N-甲基-D-天冬氨酸(NMDA)受体拮抗剂,常用于模拟精神分裂症的某些方面。

方法

将大鼠群居饲养,并植入射频识别(RFID)标签。每个饲养笼都放置在 RFID 读取器基板上,以自动监测每只大鼠的社交和运动活动。所有大鼠在给予生理盐水和 PCP(2.5mg/kg)后均进行 24 小时饲养笼内数据采集。

结果

PCP 导致注射后 15 至 60 分钟内的运动距离显著增加。此外,PCP 显著增加了大鼠与笼内同伴隔离的时间,这种社交隔离发生在治疗后 60 至 105 分钟。

结论

与传统的检测方法不同,笼内监测可捕捉到同一组动物中药物对多种行为的时间持续效应。这种方法可以通过提高动物福利和增加实验室间的可重复性,从而有益于精神药理学的药物发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/7675779/124b66e1d928/10.1177_0269881120920455-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/7675779/8d62915bc15c/10.1177_0269881120920455-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/7675779/124b66e1d928/10.1177_0269881120920455-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/7675779/8d62915bc15c/10.1177_0269881120920455-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a15/7675779/124b66e1d928/10.1177_0269881120920455-fig2.jpg

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