Let's get wild: A review of free-ranging rat assays as context-enriched supplements to traditional laboratory models

Abstract

More than 24,000 rodent studies are published annually, with the vast majority of these studies focused on genetically undiverse animals in highly-controlled laboratory settings. However, findings from the laboratory have become increasingly unreliable for predicting outcomes in field and clinical settings, leading to a perceived crisis in translational research. One cause of this disparity might be that most human societies, in contrast to laboratory rodents, are genetically diverse and live in super-enriched environments. Methods for importing wild rats into the laboratory, and also exporting laboratory-style chambers into natural environments are not well-known outside their respective disciplines. Therefore, we have reviewed the current status of supplements to the laboratory rodent assay. We progress logically from highly-controlled experiments with natural breeding colonies to purely naturalistic approaches with free-ranging rats. We then highlight a number of approaches that allow genetically-diverse wild rats to be utilized in context-enriched paradigms. While considering the benefits and shortcomings of each available approach, we detail protocols for random sampling, remote-sensing, and deployment of laboratory chambers in the field. As supplements to standardized laboratory trials, some of these assays could offer key insights to help unify outcomes between laboratory and field studies. However, we note several outstanding questions that must be addressed such as: the trade-off between control and context, possible reductions in sample size, ramifications for the 'standardization fallacy', and ethical dilemmas of working with wild animals. Given these challenges, further innovation will be required before supplemental assays can be made broadly-accessible and thus, transferrable across disciplines.

Keywords: Appetitive/aversive drives; Bench-to-bedside-gap; Lab-to-field studies; Naturalistic studies; Norway rats; Rattus norvegicus; Translational medicine.