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

Strekalova T, Couch Y, Kholod N, Boyks M, Malin D, Leprince P, Steinbusch HM - Behav Brain Funct (2011)

Bottom Line: 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.This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands. t.strekalova@maastrichtuniversity.nl

ABSTRACT
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.

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Chronic stress results in decreased sucrose preference in a subgroup of mice. After initial increase in sucrose preference on the 3rd week of stress, by the termination of a 4-week stress, a cohort of mice display a prominent decrease in sucrose preference. Mice subjected to chronic stress were split into anhedonic and non-anhedonic subgroups according to the criterion of 65% preference for sucrose solution (see the text), Reproduction of this material is permitted by Macmillan Publishers Ltd.
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Figure 1: Chronic stress results in decreased sucrose preference in a subgroup of mice. After initial increase in sucrose preference on the 3rd week of stress, by the termination of a 4-week stress, a cohort of mice display a prominent decrease in sucrose preference. Mice subjected to chronic stress were split into anhedonic and non-anhedonic subgroups according to the criterion of 65% preference for sucrose solution (see the text), Reproduction of this material is permitted by Macmillan Publishers Ltd.

Mentions: Numerous findings show a remarkable inter-individual variability in animals' responses to stress [9,13,41-43]. Using a principle of the isolation of responders and non-responders, we have established a mouse model of stress-induced anhedonia with an internal control for the effects of stress alone [44]. A four week chronic stress paradigm, comprised of exposing male 3-months-old C57/BL6N mice to tail suspension and restraint stress in different procedural variants resulted in a decrease of preference to 1% sucrose solution by ≤ 65% in 50-70% of animals [[44-49]; Figure 1]. It was shown that sucrose preference is similar in control, non-anhedonic and anhedonic mice before the onset of stress. At the end of the stress induction period sucrose preference and intake markedly decrease and are replaced by an increase in water consumption.


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

Strekalova T, Couch Y, Kholod N, Boyks M, Malin D, Leprince P, Steinbusch HM - Behav Brain Funct (2011)

Chronic stress results in decreased sucrose preference in a subgroup of mice. After initial increase in sucrose preference on the 3rd week of stress, by the termination of a 4-week stress, a cohort of mice display a prominent decrease in sucrose preference. Mice subjected to chronic stress were split into anhedonic and non-anhedonic subgroups according to the criterion of 65% preference for sucrose solution (see the text), Reproduction of this material is permitted by Macmillan Publishers Ltd.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3111355&req=5

Figure 1: Chronic stress results in decreased sucrose preference in a subgroup of mice. After initial increase in sucrose preference on the 3rd week of stress, by the termination of a 4-week stress, a cohort of mice display a prominent decrease in sucrose preference. Mice subjected to chronic stress were split into anhedonic and non-anhedonic subgroups according to the criterion of 65% preference for sucrose solution (see the text), Reproduction of this material is permitted by Macmillan Publishers Ltd.
Mentions: Numerous findings show a remarkable inter-individual variability in animals' responses to stress [9,13,41-43]. Using a principle of the isolation of responders and non-responders, we have established a mouse model of stress-induced anhedonia with an internal control for the effects of stress alone [44]. A four week chronic stress paradigm, comprised of exposing male 3-months-old C57/BL6N mice to tail suspension and restraint stress in different procedural variants resulted in a decrease of preference to 1% sucrose solution by ≤ 65% in 50-70% of animals [[44-49]; Figure 1]. It was shown that sucrose preference is similar in control, non-anhedonic and anhedonic mice before the onset of stress. At the end of the stress induction period sucrose preference and intake markedly decrease and are replaced by an increase in water consumption.

Bottom Line: 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.This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands. t.strekalova@maastrichtuniversity.nl

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus