Ketamine improves anhedonic phenotypes across species: Translational evidence from the Probabilistic Reward Task
medRxiv Preprint Server – June 02, 2025
Source: medRxiv
Summary
Remarkably, ketamine's ability to boost mood in severe depression may stem from its impact on how we experience pleasure. Researchers investigated if a single, low dose of ketamine could improve reward responsiveness in both patients with treatment-resistant depression and stressed rats. Using functionally identical tasks, a significant enhancement in reward processing was observed across both species. This robustly demonstrates that ketamine effectively restores the capacity for reward, offering a powerful new approach for those struggling with anhedonia.
Abstract
Background Ketamine is increasingly used as a therapeutic option for treatment-resistant depression (TRD) due to its rapid antidepressant properties, yet the mechanisms underlying these effects remain elusive. Preclinical evidence suggests ketamine acts on neural pathways implicated in reward processing, but translational efforts have proven challenging, due to a lack of paradigms allowing for analogous assessment of depressive phenotypes across species. Here, we investigated the effects of a single, subanesthetic dose of ketamine on reward responsiveness in individuals with TRD and chronically-stressed rats using functionally identical tasks.