Taming anxiety in laboratory mice

Mammalian Behaviour and Evolution Group, Institute of Integrative Biology, University of Liverpool, Leahurst Campus, Neston, UK.
Nature Methods (Impact Factor: 32.07). 10/2010; 7(10):825-6. DOI: 10.1038/nmeth.1500
Source: PubMed


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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    • "Finally, we show that the cup/massage method reduces corticosterone responses to a novel EPM exposure, suggesting that this protocol is sufficient to reduce the HPA axis response to a stressor. The cup handling advocated by Hurst and West [21] and expanded on by Gouveia and West [16] demonstrated anxiety-reducing effects of the cup method. "
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    ABSTRACT: Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). Copyright © 2015. Published by Elsevier Inc.
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    • "For example, stress can result in neophobia (Ennaceur et al., 2009), and so even the relatively small amount of stress that may be induced through handling (which may be considerable in these one trial a day tasks as animals are repeatedly taken in and out of the apparatus) may be sufficient to drive behaviour away from the novel stimulus, thereby masking true recognition abilities. Recent evidence supports this view and suggests that particular animal handling procedures can induce aversion and anxiety which can subsequently influence performance in behavioural tasks (Hurst and West, 2010). In this study, mice demonstrated greater anxiety in an elevated plus maze through reduced entry to the arms without protective walls when they were commonly handled with more anxiety-provoking methods such as being picked up by the tail. "
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    Neuroscience & Biobehavioral Reviews 04/2015; 53. DOI:10.1016/j.neubiorev.2015.03.013 · 8.80 Impact Factor
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    • "Knowledge about animals ' physical and behavioral requirements , and the welfare impact of scientific procedures , is expanding rapidly and being translated into practical information to minimize pain and distress and improve the robustness and reproducibility of animal experiments . For example , novel hand - ling methods for mice which avoid the high anxiety and variation associated with traditional methods ( Hurst and West , 2010 ) , use of ' grimace scales ' to assess post - surgical pain in animals , so that it can be alleviated and its potentially confounding effects removed ( Keating et al . , 2012 ; Leach et al . "
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