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.
A single low dose of ketamine (0.5 mg/kg) reduced depressive, anhedonic, and ruminative symptoms 24 hours later in 24 people with treatment-resistant depression. The symptom improvement was not linked to changes in brain connectivity but was associated with connectivity patterns present before the infusion. After ketamine, participants showed broad increases in resting-state functional connectivity within and between the default mode and frontoparietal networks, as measured by EEG. The authors suggest these connectivity increases may reflect ketamine's synaptogenic effects, which can be short-lived. The study included 34 healthy controls who did not receive ketamine.