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Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice

Lab Animal volume 40, pages 119–128 (2011)Cite this article

Abstract

Routine laboratory procedures, such as handling or transporting animals or carrying out injections on animals, are stressful for animals but are necessary in many pre-clinical studies. Here, the authors show that multiple injections of the non-toxic vehicle cyclodextrin moderately increased plasma corticosterone concentrations in female BALB/c mice. Additionally, male BALB/c mice that had received a single intraperitoneal injection of harmless saline had an increased glucocorticoid response to a second saline injection. The authors found that female mice that had been exposed to an acute psychological stress session had a decreased glucocorticoid response to a second homotypic stressor. In contrast, multiple psychological stress sessions led to increased glucocorticoid release in female mice. Acute injection(s) of saline in male mice and of cyclodextrin in female mice led to transient lymphocytopenia. Further analysis showed that repeated stress–induced lymphocytopenia is glucocorticoid-dependent. The authors conclude that laboratory stress can affect physiological parameters in mice, potentially altering study results.

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Figure 1: Average plasma corticosterone concentrations in female BALB/c mice in response to repeated injections (experiment 1).
Figure 2: Average plasma corticosterone concentrations in female BALB/c mice in response to acute psychological stress (experiment 2).
Figure 3: Average plasma corticosterone concentrations in male BALB/c mice in response to saline injection(s) (experiment 3).
Figure 4: Average whole blood lymphocyte numbers in female BALB/c mice in response to acute psychological stress (experiment 2).
Figure 5: Average whole blood lymphocyte numbers in male BALB/c mice in response to saline injection(s) (experiment 3).
Figure 6: Average whole blood lymphocyte numbers in female BALB/c mice in response to acute stress, repeated stress or dexamethasone treatment (experiments 1 and 2).

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Acknowledgements

The work was supported by the Deutsche Forschungsgemeinschaft (DFG, GRK-840, projects B1, C1), the Fonds der Chemischen Industrie (C.S.) and the Alfried Krupp von Bohlen and Halbach Stiftung, Essen, Germany (C.S.).

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Author notes

  1. Solveig Drude and Annett Geißler: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Ernst-Moritz-Arndt-University, Greifswald, Germany

    Solveig Drude, Annett Geißler, Jakob Olfe,  Astrid Starke, Grazyna Domanska,  Christine Schuett &  Cornelia Kiank-Nussbaum

  2. Institute of Physiology, University of Zurich, Zurich, Switzerland

    Astrid Starke

  3. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

    Astrid Starke

  4. AtomRain, Los Angeles, CA

    Cornelia Kiank-Nussbaum

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Correspondence to Cornelia Kiank-Nussbaum.

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Drude, S., Geißler, A., Olfe, J. et al. Side effects of control treatment can conceal experimental data when studying stress responses to injection and psychological stress in mice. Lab Anim 40, 119–128 (2011). https://doi.org/10.1038/laban0411-119

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