Open Access Highly Accessed Review

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

Tatyana Strekalova12*, Yvonne Couch3, Natalia Kholod14, Marco Boyks1, Dmitry Malin5, Pierre Leprince6 and Harry MW Steinbusch1

Author Affiliations

1 Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands

2 Center of Environmental Biology, Faculty of Sciences, Lisbon University, Lisbon, Portugal

3 Department of Pharmacology, Oxford University, Oxford, UK

4 Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia

5 Northwestern University, Feinberg School of Medicine, Lurie Cancer center, Chicago, IL, USA

6 GIGA-Neuroscience, University of Liege, Liege, Belgium

For all author emails, please log on.

Behavioral and Brain Functions 2011, 7:9  doi:10.1186/1744-9081-7-9

Published: 27 April 2011


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.

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