Discouraged zebrafish help reveal how ketamine works in the brain

Ketamine acts on astroglia in the brain, and that astroglial activity can change how animals respond to futility-like situations. Researchers used a zebrafish “giving up” behavior, where fish stop swimming when virtual reality feedback shows they are not progressing. A brief ketamine exposure suppressed this passivity for over a day, making fish less likely to give up even when movement was ineffective. Whole-brain imaging showed ketamine increased calcium activity in astroglia. The proposed mechanism is that ketamine overstimulates astroglia, which then become less sensitive to the future futility signal. The study reports similar astrocyte activation in mice, suggesting a conserved ketamine-astroglia mechanism that could inform future depression treatments.