Exploring persistence in animal models: The sinking platform test.

Abstract

Persistence is the capacity to sustain goal-oriented behavior despite recurring obstacles and setbacks. Recent studies have underscored the importance of this attribute as an integral facet of resilience and a protective factor against depression. In animal models, persistence is commonly examined through operant paradigms, wherein it is operationalized as resistance to the extinction of reward-directed actions. However, these methods are labor-intensive and resource-demanding, prompting questions about their efficiency in exploring the biological underpinnings of persistence and evaluating pharmacological interventions. To address these challenges, our team developed the Sinking Platform Test (SPT), a high-throughput animal task designed to assess persistence under stressful conditions. In the SPT, mice are trained to escape from a water-filled tank by climbing onto a platform above the water. Training also encompasses occasional "failure trials", where the platform is submerged after being climbed, compelling the mice to locate and ascend a new platform. The final test consists of a 5-minute session exclusively comprising failure trials, and persistence is measured as the number of climbed platforms. Our research revealed that chronic stress diminishes performance in the SPT, an effect reversed by chronic antidepressant treatment or voluntary exercise. These findings highlight the potential of SPT for investigating persistence and exploring its role in resilience and depression. Ongoing efforts within our laboratory focus on refining the SPT to minimize stress while enhancing methodological rigor and reproducibility, notably through automation. Future research endeavors will aim to improve SPT's translational relevance by adapting the paradigm for human application, potentially leveraging virtual-reality technologies.