Conditioning properties of social subordination in rats: Behavioral and biochemical correlates of anxiety

To develop a socially based model of anxiety, the contextual fear conditioning properties of social defeat were examined in rats. Social threat consisted of exposing intruders to aggressive residents in resident home cage, separated by a partition. During 3 daily encounters, intruders were either defeated or threatened by residents, providing the defeated–threatened (DT) and threatened–threatened (TT) groups respectively. On Day 4, both DT and TT animals were subjected to a social threat only. Additional animals received a 4-day exposure to a novel empty cage (EC group). Further DT, TT, and EC rats were confronted to a different context on Day 4. DT rats exhibited a robust and context-specific anxiety-like response, characterized by significant behavioral and biochemical alterations. DT rats showed increased risk assessment and decreased exploration compared to TT and EC rats that in turn were not different towards each other. DT and TT rats exhibited increased ACTH levels, while only DT rats showed enhanced corticosterone and decreased testosterone levels compared to EC. These differences were context-specific since they were absent confronting animals to a different context and since they were not long lasting. Overall, these data demonstrate the induction of an anxiety-like state in rats through a context conditioning process based upon social factors. The social basis of this paradigm offers good face validity with anxiety disorders, which in humans are mainly related to social factors and associated with HPA axis deregulations. The present procedure may provide a useful experimental model to further investigate the neurobiological mechanisms underlying anxiety-related disorders.