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Taming anxiety in laboratory mice


Routine laboratory animal handling has profound effects on their anxiety and stress responses, but little is known about the impact of handling method. We found that picking up mice by the tail induced aversion and high anxiety, whereas use of tunnels or open hand led to voluntary approach, low anxiety and acceptance of physical restraint. Using the latter methods, one can minimize a widespread source of anxiety in laboratory mice.

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Figure 1: Effect of handling method on voluntary interaction with the handler and behavior in an elevated plus maze, tested during the dark phase of the diurnal cycle.
Figure 2: Voluntary interaction with the handler after restraint by the scruff for mice experienced with different handling methods.


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We thank R. Beynon, F. Fair, J. Waters, S. Roberts, M. Garratt, J.-F. Lemaitre, S. Ramm, M. Thom, S. Rounding and R. Humphries for practical assistance, and R. Beynon, P. Stockley, S. Roberts and J. Rees for comments on a draft manuscript. The study was funded by the Biotechnology and Biological Sciences Research Council, the National Centre for the Replacement, Refinement and Reduction of Animals in Research, the Wellcome Trust and the Association for the Study of Animal Behaviour.

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Authors and Affiliations



J.L.H. gained the funding and designed the project with contributions from R.S.W.; J.L.H. and R.S.W. collected data; and J.L.H. supervised all aspects of the work, analyzed the data and wrote the manuscript.

Corresponding author

Correspondence to Jane L Hurst.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Tables 1–5 (PDF 1665 kb)

Supplementary Movie 1

Example of the tail handling method. (MOV 2842 kb)

Supplementary Movie 2

Example of the tunnel handling method. (MOV 3685 kb)

Supplementary Movie 3

Example of the cup handling method on day 1 and on subsequent days. (MOV 5425 kb)

Supplementary Movie 4

Voluntary interaction after tail handling. Typical responses of BALB/c, C57BL/6 and ICR(CD-1) mice after handling in the ninth session. (MOV 7234 kb)

Supplementary Movie 5

Voluntary interaction after tunnel handling. Typical responses of BALB/c, C57BL/6 and ICR(CD-1) mice after handling in the ninth session. (MOV 6835 kb)

Supplementary Movie 6

Voluntary interaction after cup handling. Typical responses of BALB/c, C57BL/6 and ICR(CD-1) mice after handling in the ninth session. (MOV 7251 kb)

Supplementary Movie 7

Examples of first transfer from tunnel to hand using the combined method for C57BL/6 mice. (MOV 5429 kb)

Supplementary Movie 8

Voluntary interaction after combined tunnel to cup handling. Typical responses of C57BL/6 mice after direct cup handling in the ninth session. (MOV 5465 kb)

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Hurst, J., West, R. Taming anxiety in laboratory mice. Nat Methods 7, 825–826 (2010).

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