Vulnerability to chronic subordination stress-induced depression-like disorders in adult 129SvEv male mice

Harold Dadomo, Valentina Sanghez, Luisana Di Cristo, Andrea Lori, Graziano Ceresini, Isabelle Malinge, Stefano Parmigiani, Paola Palanza, Malcolm Sheardown, Alessandro Bartolomucci

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders.

Original languageEnglish (US)
Pages (from-to)1461-1471
Number of pages11
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume35
Issue number6
DOIs
StatePublished - Aug 1 2011

Bibliographical note

Funding Information:
Financially supported by Takeda Cambridge Ltd (PP, AB) and the University of Parma (FIL 2008 to PP and SP).

Keywords

  • Anhedonia
  • Anxiety
  • Knockout mice
  • Major depression
  • Strain comparison
  • Stress

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