Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal

Psychoneuroendocrinology. 2008 Nov;33(10):1357-68. doi: 10.1016/j.psyneuen.2008.07.010. Epub 2008 Sep 13.


Etiopathogenesis of depression and the cause of insensitivity to treatment remain poorly understood, although genetic makeup has been established as a contributing factor. The isogenicity of inbred mouse strains provides a useful tool for investigating the link between genes and behavior or drug response. Hence, our aim was to identify inbred mouse strains (among A/J, BALB/c, C3H, C57BL/6, CBA, DBA and FVB) sensitive to a 9-week period of unpredictable chronic mild stress (UCMS) and, from the fifth week onward, to the reversal effect of an antidepressant (AD) (imipramine, 20mg/kg/day i.p.) on various depression-related changes: physical, behavioral and neuroendocrine states. UCMS induced a significant deterioration of the coat state (in all the strains), blunted emotional reactivity in the novelty-suppressed feeding (NSF) test (A/J, BALB/c, C57BL/6), and changes in the level of fecal corticosterone metabolites (BALB/c, C57BL/6, DBA, FVB). Imipramine treatment reversed the UCMS-induced alterations of the coat state (BALB/c, DBA), in the NSF test (A/J, BALB/c, C57BL/6) and in fecal corticosterone metabolites (BALB/c, C57BL/6). C3H, CBA and FVB mice were irresponsive to imipramine treatment. It is noteworthy that UCMS-induced physical or behavioral changes occurred without hypothalamo-pituitary-adrenal (HPA) axis alterations in some strains (A/J, C3H, CBA), although the AD-induced reversal of these changes in BALB/c and C57BL/6 was associated with HPA axis normalization. Finally, UCMS is shown to discriminate various alterations and to replicate in a strain-dependent manner diverse profiles reminiscent of human disease subtypes. UCMS may thus enable the selection of strains suitable for investigating specific depression-related features and could be an appropriate model for identifying genetic factors associated with increased vulnerability, specific symptoms of affective disorders, and AD resistance.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Body Weight / physiology
  • Depression / drug therapy*
  • Depression / genetics*
  • Depression / psychology
  • Exploratory Behavior / physiology
  • Feces / chemistry
  • Hair / physiology
  • Imipramine / therapeutic use
  • Male
  • Mice
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Species Specificity
  • Stress, Psychological / psychology


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Imipramine