Ketamine improves anhedonic phenotypes across species: Translational evidence from the Probabilistic Reward Task
Mario Bogdanov, Jason N. Scott, Shiba M. Esfand, Brian W. Boyle, Ty Lees, Mohan Li, Sarah E. Woronko, Samantha R. Linton, Amaya R. Jenkins, Courtney Miller, Shuang Li, Paula Bolton, Daniela B. Radl, Thomas J. Kornecook, Robert C. Meisner, Brian D. Kangas, Diego A. Pizzagalli
medRxiv Preprint Server June 2, 2025 preprint DOI: 10.1101/2025.06.02.25328447 via medRxiv
Summary
AI-generated from the abstractA single, subanesthetic dose of ketamine improved reward responsiveness in both humans with treatment-resistant depression and chronically-stressed rats, measured using functionally identical tasks. The finding suggests that ketamine's rapid antidepressant effects may involve enhancing reward processing, a core feature of anhedonia. The work provides translational evidence linking preclinical and clinical observations, though the mechanisms remain unclear.
Study at a glance
| Characteristics | Translational study with experimental treatment |
|---|---|
| Population | Individuals with treatment-resistant depression and chronically-stressed rats |
| Intervention | Ketamine |
| Dose | subanesthetic dose |
| Topics | Depression Ketamine |
| Keywords | Ketamine treatment Ketamine therapy Severe depression Mood disorder |
| Citations | 1 |
| Key finding | A single subanesthetic dose of ketamine improved reward responsiveness in both humans with treatment-resistant depression and chronically-stressed rats. |
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.