Chronic social defeat stress induces context avoidance in mice

The scrutiny of social anxiety symptoms is necessary to overcome the obstacles encountered when managing this condition. Thus, it is important to study a new behavioral repertoire elicited by chronic social defeat stress (SDS), a social stressor, applied in a place conditioned fear protocol. In this study, we sought to develop a protocol that induced context avoidance after chronic SDS. Accordingly, the mice were re-exposed to an interaction apparatus (IA) to which they had been previously habituated. Between habituation and re-exposure phases, the mice were subjected to aggressive (stressed) or non-aggressive (control) encounters performed either in the IA (Exp. 1) or in a different apparatus (named social interaction box [SIB] - Exp. 2). To behaviorally assess this protocol, the mice were recorded based on spatiotemporal measures (frequency of entry and time spent in the home cage, tunnel, and surface [where the encounter took place] of the IA) and complementary measures (e.g., frequency of stretch-attend posture [SAP], rearing, and grooming). The results showed that defeated animals spent less time in the surface of the IA during the re-exposure phase as compared to the control group (Exp.1) or to conspecifics defeated elsewhere (Exp.2). In addition, these animals also presented increased number of risk assessment behavior (higher frequency of SAP) during the re-exposure phase, in comparison with its control group and mice defeated in the SIB. This shows an unprecedented place-dependent SDS-induced context avoidance. Taken together, the present study offers a relatively simple protocol capable of eliciting context avoidance induced by chronic SDS. It accounts for a novel behavioral repertoire that might be further explored within the scope of social affective disorders.