Social defeat-induced contextual conditioning differentially imprints behavioural and adrenal reactivity: a time-course study in the rat.

Background: One of the major sources of stress in most species including humans is of a social nature. In humans social conflicts may originate sequelae of negative emotions eventually leading to isolation, anxiety and depression. The present experiments were based on the rat resident-intruder paradigm which is one of the better characterized animal models for social stress. The aim of the studies was to better understand how social stress experiences may determine persisting behavioural and physiological changes, relevant for the development and maintenance of symptoms related to human psychopathologies such as anxiety and depression. In the present study, the temporal dynamics of this social stress were examined, focusing on the long term conditioning properties of social defeat. Methods: Male Sprague-Dawley intruder rats were exposed to aggressive conspecific residents. During 3 daily 30 min encounters, intruders were either defeated or threatened by residents, providing the defeated-threatened (DT) and threatened-threatened (TT) groups respectively, or exposed to a novel empty cage (EC). The effect of such exposures on both behaviour and hypothalamo–pituitary–adrenal (HPA) axis parameters were assessed in 3 separate experiments 8, 14, or 21 days following the last session, by exposing subject animals to either a threatening resident (DT and TT groups) or to an empty cage (EC group) for 15 min. Results: A specific and persistent behavioural conditioning was observed for both socially defeated animals and animals exposed only to social threat, highlighting a lack of habituation for the conditioning properties of this social stressor. At all timepoints examined, spatial and social exploration were decreased in DT (p<0.0001) and TT rats (p<0.01) compared to EC rats. Furthermore, defensive behaviors were significantly increased in DT intruders compared to either TT (p<0.05) or EC (p<0.01) rats. Anxiety-related behaviours were displayed by TT intruders as was shown by the increased self-grooming behaviour in TT compared to both DT and EC animals (p<0.05). Regarding HPA axis hormones, differences across the groups were found onlywhen rats were exposed to the conditioning context 21 days after the last conditioning experience: higher ACTH and corticosterone levels were found comparing both DT (p<0.001; p<0.01) and TT (p<0.001; p<0.01) to EC animals, suggesting the occurrence of habituation in the EC animals only. Conclusions: These data give further support to the lasting effects of this social stress model, bestowing a special emphasis upon the impact of its psychological component and upon the relevance of its development and maintenance over time. Future studies will investigate the mechanisms underlying the development and maintenance of the observed changes by the examination of the neuroplasticity of brain areas known to be involved in the stress response. Such studies may provide a test system to investigate the biological basis of social stress-related psychopathologies.