UC San Diego

Major depressive disorder (MDD) is a common leading cause of disability worldwide, yet it is estimated that one-third of patients are treatment-resistant given the current MDD therapies. A core feature of MDD is anhedonia, the reduced ability to experience pleasure or hedonic feelings in response to formerly rewarding stimuli. Ketamine, a non-competitive NMDAR antagonist, gained approval as an antidepressant and has been shown to reduce anhedonic symptoms and restore behavioral activity. To investigate the stress-induced subject’s response to reward across time, specifically how anhedonic classifications behaviorally interplay with reward, we implemented the chronic mild stress (CMS) protocol to induce anhedonia in male mice. Anhedonic classifications, resilient and susceptible, were based on the sucrose preference score and determined via k-means clustering. We utilized in vivo two-photon calcium imaging to record the behavioral (lick probability) data. Our results show no association between stress and reward consumption when compared to control subjects at any of the investigated time points. However, a significant correlation between lick probability and sucrose preference score was observed specifically within the post-stress cue onset and ketamine cue onset. These results pose a first step into unveiling and better understanding the correlation between anhedonic phenotypes and the prospective response to positive stimuli.