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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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Anhedonic mice display lasting increases in home cage activity during the dark phase of the day. (A) During the dark phase of the diurnal cycle, mean time of horizontal movement of the anhedonic group (dashed line) is significantly elevated during 2nd-4th weeks of stress, and during weeks 1 and 2 after the termination of the stress procedure, as compared to the non-anhedonic (plain thick line) and control (plain thin line) groups (*p < 0.05 vs. control group and # p < 0.05 vs. non-anhedonic group; Mann-Whitney). This parameter does not change in the non-anhedonic group throughout the entire experiment (p > 0.05 vs. control group). (B) During the light phase of the day, no difference between the groups in home cage activity is observed (p > 0.05). Data are expressed as mean ± (SEM).
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Figure 4: Anhedonic mice display lasting increases in home cage activity during the dark phase of the day. (A) During the dark phase of the diurnal cycle, mean time of horizontal movement of the anhedonic group (dashed line) is significantly elevated during 2nd-4th weeks of stress, and during weeks 1 and 2 after the termination of the stress procedure, as compared to the non-anhedonic (plain thick line) and control (plain thin line) groups (*p < 0.05 vs. control group and # p < 0.05 vs. non-anhedonic group; Mann-Whitney). This parameter does not change in the non-anhedonic group throughout the entire experiment (p > 0.05 vs. control group). (B) During the light phase of the day, no difference between the groups in home cage activity is observed (p > 0.05). Data are expressed as mean ± (SEM).

Mentions: Mean duration of movement was significantly elevated, in anhedonic animals only, during the dark phase of the day/night cycle between days 14 and 21 during the stress procedure and for at least 14 days after termination of the procedure (Figure 4A); no differences between the groups are observed during the light phase (Figure 4B).


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)

Anhedonic mice display lasting increases in home cage activity during the dark phase of the day. (A) During the dark phase of the diurnal cycle, mean time of horizontal movement of the anhedonic group (dashed line) is significantly elevated during 2nd-4th weeks of stress, and during weeks 1 and 2 after the termination of the stress procedure, as compared to the non-anhedonic (plain thick line) and control (plain thin line) groups (*p < 0.05 vs. control group and # p < 0.05 vs. non-anhedonic group; Mann-Whitney). This parameter does not change in the non-anhedonic group throughout the entire experiment (p > 0.05 vs. control group). (B) During the light phase of the day, no difference between the groups in home cage activity is observed (p > 0.05). Data are expressed as mean ± (SEM).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Anhedonic mice display lasting increases in home cage activity during the dark phase of the day. (A) During the dark phase of the diurnal cycle, mean time of horizontal movement of the anhedonic group (dashed line) is significantly elevated during 2nd-4th weeks of stress, and during weeks 1 and 2 after the termination of the stress procedure, as compared to the non-anhedonic (plain thick line) and control (plain thin line) groups (*p < 0.05 vs. control group and # p < 0.05 vs. non-anhedonic group; Mann-Whitney). This parameter does not change in the non-anhedonic group throughout the entire experiment (p > 0.05 vs. control group). (B) During the light phase of the day, no difference between the groups in home cage activity is observed (p > 0.05). Data are expressed as mean ± (SEM).
Mentions: Mean duration of movement was significantly elevated, in anhedonic animals only, during the dark phase of the day/night cycle between days 14 and 21 during the stress procedure and for at least 14 days after termination of the procedure (Figure 4A); no differences between the groups are observed during the light phase (Figure 4B).

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