Optimization of a panel of behavioral tests for use in containment using a golden Syrian hamster model

Golden Syrian hamsters are an often-overlooked model in behavioral testing. While previously utilized for research examining circadian rhythms and mammalian reproduction, they are less common than murine models in both infectious disease and behavioral studies. However, coronavirus disease-19 (COVID-19) quickly pushed hamster modeling to the forefront due to its myriad of advantages over mice in recapitulating human pathology and transmission. At least 10 % of COVID-19 survivors suffer from post-acute sequelae of COVID-19 (PASC), a collection of some 200 sequelae with neurologic sequelae (neuro-PASC) presenting with potentially debilitating symptomology. This presents a clear need for a small animal model that recapitulates human disease with the ability to assess any potential long term neurological changes. We adapted and optimized a panel of behavioral tests from previously accepted murine models utilizing the golden Syrian hamster model for use within biocontainment facilities. Our panel includes grip strength, Porsolt forced swim, and novel object recognition testing to measure muscle fatigue or weakness, depression, and memory loss or cognitive impairment, respectively. Apart from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), this panel of tests is applicable to other pathogens that cause neurologic sequelae, such as Nipah or eastern equine encephalitis viruses, or any other model systems that require the use of hamsters. In this manuscript, we detail the methods for each of these three behavioral tests, how to interpret and analyze the resulting data, and emphasize additional factors for consideration. We also provide baseline data for both male and female golden Syrian hamsters.