51. Developing a novel animal model of depression to study the role of inflammation in disease progression and in the mechanism of antidepressant action

Abstract

To study the role of inflammation in depression and in the mechanisms of antidepressant action a valid animal model is required. To develop such a model, we proposed to combine exposure to inflammatory stimulus modelled by peripheral lipopolysaccharide (LPS) injection with an environmental stress-based model of depression – unpredictable chronic mild stress (UCMS) to achieve an immunologically-relevant depression-like phenotype. In a pilot experiment, we treated 8 weeks old male BALB/c mice with 0.33 mg/kg LPS and subsequently exposed them to UCMS for 7 weeks. Fluoxetine-treated groups (10 mg/kg daily) were also included in our experimental design (N = 12). LPS and UCMS exposed mice displayed significant coat state deterioration (UCMS factor H (7) = 37.5, p < 0.0001) and locomotor hyperactivity in a novel arena (UCMS factor F (1,74) = 20.8, p < 0.0001). When coat state was assessed 4 days after the end of UCMS paradigm, the UCMS-only group already displayed signs of recovery with the coat deterioration score indistinguishable from control, while animals exposed to both LPS and UCMS did not show improvement of the coat state. Fluoxetine treatment of the LPS and UCMS exposed group promoted the recovery of the coat state with the coat deterioration score returning to control levels. Future assessment of the neurobiological phenotype (corticosterone response to stress, peripheral cytokines and hippocampal neurogenesis levels) will be presented to allow us to further unravel the neurobiological basis of the observed behavioural changes.