Parsons, M., Stryjek, R., Fendt, M. et al. 2023. Making a case for the free exploratory paradigm: Animal welfare-friendly assays that enhance heterozygosity and ecological validity. Frontiers in Behavioral Neuroscience 17, 1228478.

Animal welfare considerations are an essential part of scientific research. If animals may suffer, then even 26 the most promising research plans can be delayed or rejected and the resulting data may be questionable. 27 With more data supporting sentience in a variety of species, calls by advocates to ensure subjects’ well28 being will continue to increase. There is therefore a pressing need to develop new approaches to limit 29 suffering in research. This is especially true in rodents, which comprise 90% of all animal research 30 subjects. Over the past fifteen years, the evidence for sophisticated cognitive abilities and behavioral 31 plasticity has increased substantially: some rodents have social justice, drive robotic cars and move to the 32 rhythm of music. Some common and traditional assays however, continue to rely on injurious approaches 33 that may include starving, drowning, and other deprivations. These tests may not be necessary, and 34 inferences coming from highly stressed animals may be incorrect. Common drawbacks to subjects in 35 laboratory tests include a lack of genetic variability (heterozygosity), epigenetic changes, inbred 36 ‘degenerate’ lines with altered physiology and cognition, and the unnatural contexts created by laboratory 37 conditions which create ecological mismatches for evolved cognitive processes. Here, we argue that the 38 free exploratory paradigm (FEP) can be used in the wild or in the laboratory, whereby animals are not 39 starved, may not be isolated from shelter or conspecifics, and subjects have the ability to participate or 40 leave the test when they want. The FEP in the wild can help improve research outcomes because subjects 41 are tested in more natural ‘evolved’ conditions, subjects are likely more genetically variable, and humans 42 are not actively handling them. In the laboratory, many of these same benefits can be realized, particularly 43 when using wild animals, which may be acceptable in certain situations. We outline some of the benefits 44 of the most accessible or popular FEP assays for neuroscience, while considering the implications for 45 animal welfare. While these designs will not be universally applicable, when used they will reduce 46 suffering and may increase the validity and generalizations of research inferences.