Update in the methodology of the chronic stress paradigm: internal control matters

Tatyana Strekalova*, Yvonne Couch, Natalia Kholod, Marco Boyks, Dmitry Malin, Pierre Leprince, Harry M. W. Steinbusch

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

110 Citations (Web of Science)


To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals.
Original languageEnglish
Pages (from-to)18
JournalBehavioral and brain functions
Publication statusPublished - 27 Apr 2011


  • animal model of depression chronic stress
  • sucrose test
  • anhedonia
  • antidepressant treatment
  • gene expression profiling
  • neuroinflammation
  • mouse

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