Ketamine produces short-lived increases in reward responsiveness in rats under nonstressful conditions, but under ongoing chronic stress it rescues blunted reward responsiveness for nearly one week. These findings highlight the role of environmental context in ketamine's effects on reward processing and suggest its antianhedonic action may contribute to its antidepressant efficacy.
A single low dose of ketamine improves the ability to learn from rewards in both people with treatment-resistant depression and stressed rats, using nearly identical tasks. Twenty-four hours after receiving ketamine, individuals with treatment-resistant depression and chronically stressed rats showed a stronger tendency to choose the more frequently rewarded option, matching the performance of healthy controls. This effect was most pronounced in people with more severe anhedonia at the start. Ketamine did not affect general task accuracy, indicating it selectively boosts reward learning rather than overall performance. These findings point to a shared behavioral mechanism by which ketamine alleviates anhedonia, with potential implications for treating anhedonia in depression and related conditions.