Abstract
Inter-individual variability in quantitative traits is believed to potentially inflate the quality of results in animal experimentation. Yet, to our knowledge this effect has not been empirically tested. Here we test whether inter-individual variability in emotional response within mouse inbred strains affects the outcome of a pharmacological experiment. Three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, five consecutive trials). A multivariate clustering procedure yielded two multidimensional response types which were displayed by individuals of all three strains. We show that systematic incorporation of these individual response types in the design of a pharmacological experiment produces different results from an experimental pool in which this variation was not accounted for. To our knowledge, this is the first study that empirically confirms that inter-individual variability affects the interpretation of behavioral phenotypes and may obscure experimental results in a pharmacological experiment.
Highlights
In preclinical experimental animal research, inter-individual variability in phenotypic response is a major source of within-group variability that may negatively affect the power of animal experiments and the reproducibility of their outcomes [1,2,3]
We explored whether incorporating these individual response types in the design of a standard pharmacological experiment would affect the results in comparison to an experiment in which this variation was not controlled for
A 2 x 3 x 2 factorial complete randomized block design was used to test the effect of dexmedetomidine on behavior in the modified Hole Board (mHB)
Summary
In preclinical experimental animal research, inter-individual variability in phenotypic response is a major source of within-group variability that may negatively affect the power of animal experiments and the reproducibility of their outcomes [1,2,3]. The exact constitution of inter-individual variability ( referred to as the third component [2] or phenotypic variation [3]) is poorly understood. It is generally accepted that the expression of inter-individual variability is the net result of complex interactions between genetic and environmental factors that are partly modulated by epigenetic processes [3,4]. Quantitative traits have even been shown to vary between individuals of the same mouse inbred strain, despite extensive environmental standardization and the use of genetically and microbiologically defined mice of similar age and sex [1,3].
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