Lundberg Stina, Nylander Ingrid, Roman Erika
Research Group Neuropharmacology, Addiction and Behavior, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Division of Anatomy and Physiology, Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Front Behav Neurosci. 2020 Mar 19;14:37. doi: 10.3389/fnbeh.2020.00037. eCollection 2020.
Early-life stress and its possible correlations to genes, environment, and later health outcomes can only be studied retrospectively in humans. Animal models enable the exploration of such connections with prospective, well-controlled study designs. However, with the recent awareness of replicability issues in preclinical research, the reproducibility of results from animal models has been highlighted. The present study aims to reproduce the behavioral effects of maternal separation (MS) previously observed in the multivariate concentric square field (MCSF) test. A second objective was to replicate the adolescent behavioral profiles previously described in the MCSF test. Male rats, subjected to short or prolonged MS or standard rearing, were subjected to behavioral testing in early adolescence and early adulthood. As seen in previous studies, the behavioral effects of MS in the MCSF were small at both tested time points. When tested in early adolescence, the animals exhibited a similar behavioral profile as previously seen, and the finding of adolescent behavioral types was also reproduced. The distribution of animals into the behavioral types was different than in the initial study, but in a manner consistent with developmental theories, as the current cohort was younger than the previous. Notably, the Shelter seeker behavioral type persisted through development, while the Explorer type did not. The lack of basal behavioral effect after MS is in line with the literature on this MS paradigm; the working hypothesis is that the prolonged MS gives rise to a phenotype predisposed to negative health outcomes but which is not apparent without additional provocation.
早年生活压力及其与基因、环境和后期健康结果的可能关联，在人类中只能通过回顾性研究来探讨。动物模型能够通过前瞻性、严格控制的研究设计来探索此类联系。然而，随着近期对临床前研究中可重复性问题的认识，动物模型结果的再现性受到了关注。本研究旨在重现先前在多元同心方场（MCSF）试验中观察到的母体分离（MS）的行为效应。第二个目标是复制先前在MCSF试验中描述的青春期行为特征。对经历短期或长期MS或标准饲养的雄性大鼠，在青春期早期和成年早期进行行为测试。如先前研究所示，在两个测试时间点，MS在MCSF中的行为效应都很小。在青春期早期进行测试时，动物表现出与先前相似的行为特征，并且青春期行为类型的发现也得到了重现。动物在行为类型中的分布与最初的研究不同，但符合发育理论，因为当前队列比先前队列更年轻。值得注意的是，寻求庇护者行为类型在发育过程中持续存在，而探索者类型则不然。MS后缺乏基础行为效应与关于这种MS范式的文献一致；目前的假设是，长期MS会产生一种易患负面健康结果的表型，但在没有额外刺激的情况下并不明显。
