Chronic social defeat-induced social avoidance as a proxy of stress resilience in mice involves conditioned learning

Abstract

Chronic social defeat (CSD)-induced social avoidance is considered to model a feature of stress-related mental dysfunction, while its absence has been used as a proxy of resilience in rodents. However, knowledge on the mechanisms shaping CSD-induced individual outcomes remains fragmentary. Fear conditioning has been described as a suitable model in humans for better understanding the pathophysiology of stress related mental disorders. We sought to explore the extent to which conditioned learning is involved in CSD-induced social avoidance. In experiment 1 (social avoidance specificity), C57BL/6 J male mice underwent CSD followed by a modified social interaction test offering the simultaneous choice between an unknown mouse from the aggressor's strain or a mouse from a different strain and phenotypic characteristics. In experiment 2 (social avoidance extinction), CSD-extinction sessions involving only the sensory phase of CSD were conducted on one group of defeated mice whereas a second group only received handling, followed by social interaction test with a novel mouse from the aggressor's strain. Our results provide evidence that CSD-induced social avoidance does not generalize to other phenotypic characteristics than those of the aggressors and can be successfully reversed during extinction training. Taken together, our findings strongly point to the involvement of conditioned learning in shaping CSD-induced social avoidance, a finding that is of interest to future studies into the neurobiology of resilience.

Keywords: Chronic social defeat; Conditioned learning; Extinction; Mouse model; Social avoidance; Stress resilience.