Background

Mood and anxiety disorders have a growing prevalence, potentially affecting one out of four people during their lifetime (Anacker et al., 2018; Du et al., 2021). This could result in a great burden for the affected individuals, their families, and the society. Establishing high-validity animal models is of great importance for exploring these diseases (Becker and Wojtowicz, 2007; Anacker and Hen, 2017; Anacker et al., 2018). It has been reported that social stress plays a central role in the pathogenesis of different psychiatric disorders (Padilla-Coreano et al., 2016). Thus, scientific researchers have strived to establish animal models of social defeat that would potentially provide significant and basic information for understanding several of the physiological and behavioral abnormalities induced by social stress between individuals (Snyder et al., 2001; Golden et al., 2011; Dioli et al., 2017).

Several forms of animal models have been established, including learned helplessness, chronic unpredictable mild stress (CUMS), chronic restraint stress, chronic social defeat stress (CSDS), and others (Toyoda, 2017). Each protocol has its advantages and disadvantages. For example, the CUMS model is widely regarded as the most classic animal model of depression in use. One of its main advantages is its ability to avoid adaptive responses in animals caused by single and repetitive stimuli. However, this model also has some drawbacks, such as a lengthy modeling time and a large workload required. Our protocol is based on the CSDS model; briefly, it is established based on intermittent physical interaction between a dominant resident and a submissive intruder (Schloesser et al., 2010; Golden et al., 2011; Anacker et al., 2018).

Modifications have been made to the CSDS model according to different study aims, mainly regarding species and strains being chosen, acute or chronic exposure to stress, and the terminologies used for identifying social defeat (Anacker et al., 2016; Castilla-Ortega et al., 2016; Du et al., 2021). Here, we introduce a general procedure of a social defeat paradigm, with a focus on early-life stress. In order to enhance the aggression level of the resident mice, we chose older CD1 mice and younger C57BL/6 mice as aggressors and intruders, respectively. The C57BL/6 strain has been reported to have a greater metabolic susceptibility to social defeat stress; we chose male mice as they show territorial behavior more universally and stably than female mice. The behavioral features of social defeat are evaluated by subsequent social interaction test (SIT) and open field test (OFT). SIT is a simple test in which behaviors and staying time in the interaction and corner zones are video recorded. Compared to a normal C57 mouse, which is motivated to explore, a mouse subjected to social defeat would like to avoid the CD1 mouse in the wire mesh (Golden et al., 2011). OFT is a common measure of exploratory behavior and general activity of mice. The recording of outcomes like center time is likely to gauge some aspects of emotionality, including anxiety and depression. This model could be used for exploring specific molecular mechanisms of early-life stress-induced social defeat and depression and may open opportunities for the development of new antidepressant drugs.