Ketamine, a rapid-acting antidepressant, reduces how aversive negative outcomes feel without changing how gains are evaluated, motivation, or other learning processes. In rhesus macaques making token-based decisions, ketamine lowered the impact of losses when given intramuscularly or intranasally. This effect was separate from side effects like fixation errors, which could be countered by strong motivation. The acute reduction in negative event impact may lead to longer-term antidepressant effects by preventing the cumulative buildup of negative memories. The findings suggest that disrupting affective memory could pose challenges in treating depression and invite further study across different mood states and time scales.
Ketamine reduces the unpleasantness of negative outcomes without changing how gains are evaluated, according to a computational analysis of rhesus macaques making token-based decisions. The drug's effect on aversion was separable from side effects like fixation errors, which could be overcome with strong motivation to avoid mistakes. The authors propose that ketamine's acute dampening of negative events' impact might produce longer-term antidepressant effects by reducing the cumulative burden of slowly decaying memories of those events. They note that disruption-resistant affective memory could pose challenges in treating depression and call for further research on ketamine's action across diverse mood states and time scales.