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A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2,3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression.

Original publication

DOI

10.1016/j.bbi.2012.12.017

Type

Journal article

Journal

Brain Behav Immun

Publication Date

03/2013

Volume

29

Pages

136 - 146

Keywords

Anhedonia, Animals, Anxiety, Chronic Disease, Cytokines, DNA Primers, Depression, Food Preferences, Immunohistochemistry, Macrophage Activation, Male, Mice, Mice, Inbred C57BL, Microglia, Prefrontal Cortex, Real-Time Polymerase Chain Reaction, Serotonin Plasma Membrane Transport Proteins, Stress, Psychological, Sucrose, Swimming, Tumor Necrosis Factor-alpha