Magara Salvatore, Holst Sarah, Lundberg Stina, Roman Erika, Lindskog Maria
Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
Department of Pharmaceutical Biosciences, Uppsala University Uppsala, Sweden.
Front Behav Neurosci. 2015 Apr 21;9:89. doi: 10.3389/fnbeh.2015.00089. eCollection 2015.
Modeling depression in animals is based on the observation of behaviors interpreted as analog to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL), a rat model of depression, compared to the Sprague-Dawley (SD) rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF) and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered exploratory behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests.
动物抑郁症模型是基于对被解释为类似于人类症状的行为的观察。实验性抑郁症研究中使用的典型测试旨在产生非此即彼的结果。已知探索和应对策略与抑郁症相关,然而这些方面在动物行为测试中通常未被考虑。在这里,我们在三项独立测试中研究了弗林德斯敏感品系(FSL)大鼠,一种抑郁症大鼠模型,与斯普拉格-道利(SD)大鼠进行比较,在这些测试中允许动物表现出更广泛的行为表现。多元同心方场™(MCSF)和新笼测试在新环境中引发探索行为,而家笼变化测试在重新建立社会等级制度时引发社会行为。在MCSF测试中,与SD大鼠相比,FSL大鼠表现出较少的探索驱动力和更多的风险评估行为。当再次暴露于竞技场时,与第一次试验相比,FSL大鼠(而非SD大鼠)增加了它们的探索行为,并表现出与SD大鼠相同程度的风险评估行为。因此,当大鼠熟悉竞技场时,FSL大鼠的行为与SD大鼠的行为更相似。在新笼测试中,FSL大鼠表现出一种反应性应对方式,这与在MCSF中观察到的探索减少一致。反应性应对与较少的攻击行为相关。相应地,FSL大鼠在家笼变化测试中表现出较少的攻击行为。综上所述,我们的数据表明FSL大鼠表现出改变的探索行为和反应性应对方式。兴趣降低是抑郁症的核心症状,具有反应性应对方式的个体更容易患这种疾病。我们的结果支持将FSL大鼠用作抑郁症动物模型,并增加了我们对FSL大鼠的理解,超出了传统抑郁症相关测试所针对的行为维度。