Commentary: Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio

A recent study (Henriques-Alves and Queiroz, 2015) has critically evaluated traditional and novel behavioral endpoints in this model, calling for assessing multiple behaviors (rather than single indices) in longer test sessions to correctly interpret behavioral data. In line with the renowned psychopharmacologist Prof. Slava Lapin (" one experiment is not an experiment; one behavior is not a model "), these results also corroborate our long-held argument that reduced activity in the stimulus zone of the social defeat model may not necessarily reflect rodent depression-like state (e.g., social withdrawal), but can also be relevant to other traits, especially anxiety (Kudryavtseva et al., 1991; Kudryavtseva, 2003; Kalueff et al., 2006). It is appreciated that similar conclusions have been reached in a recent thorough study of mouse social defeat behaviors (Henriques-Alves and Queiroz, 2015). However, several additional considerations may factor into their experimental findings and data interpretation, thereby meriting further in-depth discussion here. For example, using a 5-day social defeat stress protocol, the authors suggest that anxiety-and depression-related behaviors may reflect the mouse " difficulty ... in evaluating reward and threat respectively, " p. 2 (Henriques-Alves and Queiroz, 2015). However, in our own experience with this model, 5 days of repeated confrontations may be merely insufficient to develop depression-like phenotype in mice, where much longer (typically, 20-day) periods of daily fighting are needed to evoke such In contrast, anxiety-like responses can be the likely phenotype evoked by shorter manipulations in the social defeat paradigm. For instance, 10 days of chronic social defeat stress evoke mouse anxiety-like behaviors which were corrected by anxiolytic drugs but not antidepressants (Kudryavtseva et al. it is likely that anxiety-like states (which also often manifest as reduced social investigation), rather than depression-like pathogenesis, could have been evoked in Henriques-Alves and Queiroz (2015) utilizing a similarly short 5-day repeated social stress protocol. Importantly, the social defeat stress protocol itself is subject to a substantial variance across the laboratories worldwide (Kudryavtseva, 2009; Golden et al., 2011), and these modifications