The Impact of Social and Behavioral Factors on Reproducibility in Terrestrial Vertebrate Models

Abstract

The use of animal models remains critical in preclinical and translational research. The reliability of the animal models and aspects of their validity is likely key to effective translation of findings to medicine. However, despite considerable uniformity in animal models brought about by control of genetics, there remain a number of social as well as innate and acquired behavioral characteristics of laboratory animals that may impact on research outcomes. These include the effects of strain and genetics, age and development, sex, personality and affective states, and social factors largely brought about by housing and husbandry. In addition, aspects of the testing environment may also influence research findings. A number of considerations resulting from the animals’ innate and acquired behavioral characteristics as well as their social structures are described. Suggestions for minimizing the impact of these factors on research are provided.

The use of ball pits and playpens in laboratory Lister Hooded male rats induces ultrasonic vocalisations indicating a more positive affective state and can reduce the welfare impacts of aversive procedures

“…Refined handling techniques and habituation to the researchers or animal technicians, and housing conditions, 26,27 including the use of ball pits and playpens, offer the potential to reduce the mild but cumulative negative affective experiences of rats housed in laboratory conditions, and these results provide objective data supporting the welfare benefits of ball pits and playpens. Animals living in an enriched environment with lower stress levels and improved well-being should provide a better model for research, and are likely to generate more reliable and reproducible data with less variability.…”

Advocating for Generalizability: Accepting Inherent Variability in Translation of Animal Research Outcomes

“…Recent ILAR publications provide summary overviews of important extrinsic factors like the room light cycle (80); social and behavioral factors (81); and the animal microbiota (82), which is strongly influenced by rodent chow formulations and can also vary wildly by brand and nutritional composition. Drinking water provided to laboratory animals is rarely considered in the experimental design, but recent evidence indicates that water source, microbial and chemical contaminants, and purification methods can result in potential experimental variability (83).…”

Ethology adopts the STRANGE framework for animal behaviour research, to improve reporting standards

“…Lots of people have stories to tell about particularly “cooperative” or “shy” subjects in captive populations, the difficulty of trapping some individuals in wild populations, or the effects of past experimental experience or testing protocols on behavioural performance. The STRANGE framework provides a means of formally articulating these concerns in research articles (Webster & Rutz, 2020), and is supported by other recent calls to evaluate more carefully how study outcomes are affected by subjects’ attributes (Whittaker & Hickman, 2020) and the composition of test samples (Voelkl et al, 2020). A detailed discussion of how STRANGE aims to improve reproducibility in animal behaviour research will be presented elsewhere.…”