Abstract
BackgroundThe significance of behavioral neuroscience and the validity of its animal models of human pathology largely depend on the possibility to replicate a given finding across different laboratories. Under the present test and housing conditions, this axiom fails to resist the challenge of experimental validation. When several mouse strains are tested on highly standardized behavioral test batteries in different laboratories, significant strain×lab interactions are often detected. This limitation, predominantly due to elevated within-group variability observed in control subjects, increases the number of animals needed to address fine experimental questions. Laboratory rodents display abnormal stress and fear reactions to experimental testing, which might depend on the discrepancy between the stability of the neonatal environment and the challenging nature of the adult test and housing conditions.Methodology/Principal FindingsStimulating neonatal environments (e.g. brief maternal separations, increased foraging demands or maternal corticosterone supplementation) reduce stress and fear responses in adulthood. Here we tested whether reduced fearfulness associated with experimental testing would also reduce inter-individual variation. In line with our predictions, we show that a moderate elevation in neonatal corticosterone through maternal milk significantly reduces fear responses and inter-individual variability (average 44%) in adult mouse offspring.Conclusions/SignificanceWe observed reduced variation in pain perception, novelty preference, hormonal stress response and resistance to pathogen infection. This suggests that the results of this study may apply to a relatively broad spectrum of neuro-behavioral domains. Present findings encourage a reconsideration of the basic principles of neonatal housing systems to improve the validity of experimental models and reduce the number of animals used.
Highlights
An accepted principle in science is that the outcomes of a given study should be reproducible in independent facilities if experimental conditions were kept constant
Within-group variability was able to explain about 60% of experimental variance, indicating that inter-individual variation is the main source of experimental noise in behavioral studies [2]
Dams drinking low levels of corticosterone showed intermediate levels of active maternal care compared to AFR and high levels of maternal corticosterone (H-CORT) dams, though differences were not statistically significant
Summary
An accepted principle in science is that the outcomes of a given study should be reproducible in independent facilities if experimental conditions were kept constant. In a meticulously controlled study, Crabbe and colleagues [1] tested this assumption by evaluating eight different mouse strains on a highly standardized behavioral test battery in three independent facilities. When several mouse strains are tested on highly standardized behavioral test batteries in different laboratories, significant strain6lab interactions are often detected. This limitation, predominantly due to elevated within-group variability observed in control subjects, increases the number of animals needed to address fine experimental questions. We observed reduced variation in pain perception, novelty preference, hormonal stress response and resistance to pathogen infection This suggests that the results of this study may apply to a relatively broad spectrum of neuro-behavioral domains. Present findings encourage a reconsideration of the basic principles of neonatal housing systems to improve the validity of experimental models and reduce the number of animals used
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