背景:社会压力是精神疾病发展的重要环境风险因素,包括抑郁症和焦虑症.社会应激范式通常用于大鼠和小鼠,以深入了解这些疾病的发病机理。社会不稳定压力(SIS)范式需要频繁(每周多次)引入一个或多个不熟悉的同性家庭伴侣。随后,新的社会等级制度的反复形成导致长期和不可预测的身体和社会压力。
目的:我们比较和讨论SIS方案对大鼠和小鼠的应激相关行为和生理影响,并解决由于协议可变性造成的限制。我们进一步提供实用建议,以优化SIS方案的可重复性。
方法:我们根据以下三个数据库中的PRISMA声明进行了系统审查:PubMed,WebofScience和Scopus我们的搜索策略不仅限于发表年份,还限于在同行评审期刊上发表的英文文章。搜索字词包括\"social*instab*\"AND(\"animal\"OR\"rodent\"OR\"rat*\"OR\"mouse\"或\"mouse\")。
结果:33项研究符合我们的纳入标准。15篇文章使用了SIS方案,其中每天改变两个笼子伴侣的组成,持续16天(SIS16D)。11篇文章使用了SIS方案,其中每周两次更改四个笼子伴侣的组成,共49天(SIS49D)。其余七项研究使用的SIS方案在实验持续时间或笼子交配量方面与这两种方案不同。SIS的行为影响主要通过量化抑郁样,像焦虑一样,社会-,和认知行为。SIS的生理影响主要使用代谢参数进行评估,下丘脑-垂体-肾上腺轴活动,以及神经生物学参数的评估,如神经可塑性和神经发生。
结论:较短和较长的SIS方案都会引起与抑郁和焦虑障碍的病理生理学相关的广泛的应激相关行为和生理损伤。迄今为止,SIS16D仅在大鼠中被报道,而SIS49D仅在小鼠中报道。鉴于这种物种特定的应用以及报告的SIS协议的可变性,其他研究应确定SIS效应是方案持续时间还是物种特异性.我们解决了几个问题,包括使用的SIS协议缺乏一致性,并建议实用,具体改进SIS方案的设计和报告,以提高这种病因学相关的社会压力临床前模型的标准化和可重复性。
BACKGROUND: Social stress is an important environmental risk factor for the development of psychiatric disorders, including depression and anxiety disorders. Social stress paradigms are commonly used in rats and mice to gain insight into the pathogenesis of these disorders. The social instability stress (SIS) paradigm entails frequent (up to several times a week) introduction of one or multiple unfamiliar same-sex home-cage partners. The subsequent recurring formation of a new social hierarchy results in chronic and unpredictable physical and social stress.
OBJECTIVE: We compare and discuss the stress-related behavioral and physiological impact of SIS protocols in rat and mouse, and address limitations due to protocol variability. We further provide practical recommendations to optimize reproducibility of SIS protocols.
METHODS: We conducted a systematic
review in accordance with the PRISMA statement in the following three databases: PubMed, Web of Science and Scopus. Our search strategy was not restricted to year of publication but was limited to articles in English that were published in peer-reviewed journals. Search terms included \"social* instab*\" AND (\"animal\" OR \"rodent\" OR \"rat*\" OR \"mice\" OR \"mouse\").
RESULTS: Thirty-three studies met our inclusion criteria. Fifteen articles used a SIS protocol in which the composition of two cage mates is altered daily for sixteen days (SIS16D). Eleven articles used a SIS protocol in which the composition of four cage mates is altered twice per week for 49 days (SIS49D). The remaining seven studies used SIS protocols that differed from these two protocols in experiment duration or cage mate quantity. Behavioral impact of SIS was primarily assessed by quantifying depressive-like, anxiety-like, social-, and cognitive behavior. Physiological impact of SIS was primarily assessed using metabolic parameters, hypothalamus-pituitary-adrenal axis activity, and the assessment of neurobiological parameters such as neuroplasticity and neurogenesis.
CONCLUSIONS: Both shorter and longer SIS protocols induce a wide range of stress-related behavioral and physiological impairments that are relevant for the pathophysiology of depression and anxiety disorders. To date, SIS16D has only been reported in rats, whereas SIS49D has only been reported in mice. Given this species-specific application as well as variability in reported SIS protocols, additional studies should determine whether SIS effects are protocol duration- or species-specific. We address several issues, including a lack of consistency in the used SIS protocols, and suggest practical, concrete improvements in design and reporting of SIS protocols to increase standardization and reproducibility of this etiologically relevant preclinical model of social stress.