A chronic unpredictable stress protocol to model anhedonic and resilient behaviors in C57BL/6J mice

The complexity of the depressive symptoms observed in humans makes modeling depressive behavior in rodents challenging. Here, we present a highly reproducible protocol to generate mouse models that mimic several aspects of depression, namely anhedonia and loss of motivation. We describe acclimatization of animals and baseline determination, followed by the chronic unpredictable stress (CUS) protocol to induce anhedonic and resilient behaviors. The protocol can generate anhedonic and resilient mice at roughly equal frequencies, providing a reliable model for translational research. For complete details on the use and execution of this protocol, please refer to Baczynska et al. (2022), Bijata et al. (2022), and Krzystyniak et al. (2019).