The social defeat/overcrowding murine psychosocial stress model results in a pharmacologically reversible body weight gain but not depression - related behaviours

Abstract

Depression is a highly prevalent psychiatric disorder, yet its etiology is not well understood. The validation of animal models is therefore a critical step towards advancing knowledge about the neurobiology of depression. Psychosocial stress has been promoted as a prospective animal model of depression, however, different protocols exist with variable responses, and further investigations are therefore required. We aimed to characterise the behavioural and body weight responses to the social defeat/overcrowding (SD/OC) model and to explore the effects of the antidepressant fluoxetine and the peroxynitrite scavenger, CuII(atsm), therein. Male C57BL/6JArc mice were exposed to a 19 day SD/OC protocol at two levels of aggression, determined by terminating SD bouts after one, or approximately five social defeat postures. This was followed by a battery of behavioural tests including social interaction test (SIT), locomotor activity (LMA), light-dark box test (LDB), saccharin preference test (SPT) and the forced swim test (FST). Mice were dosed daily with vehicle, fluoxetine (20 mg/kg) or CuII(atsm) (30 mg/kg) throughout the protocol. SD/OC increased body weight compared to controls, which was abolished by fluoxetine and attenuated by CuII(atsm). Weight gain specifically peaked during OC sessions but was not affected by either drug treatment. Fluoxetine reduced the number of defeat postures during fight bouts on some days. SD/OC otherwise failed to elicit depression- or anxiety-like behaviour in the tests measured. These data raise questions over the SD/OC model as an etiological model of depression-related behaviours but highlight the potential of this model for investigations into mechanisms regulating binge eating and weight gain under conditions of chronic social stress. Keywords: Psychosocial stress, Social defeat, Depression, Weight gain, Fluoxetine, CuII(atsm)