A single dose of psilocybin reduces reward-seeking behavior by altering inhibitory brain cells in the prefrontal cortex, with effects linked to SST interneurons

Psilocybin reduces reward-seeking behavior after a single dose by changing how inhibitory brain cells function in the prefrontal cortex. The central mechanism involves somatostatin-expressing interneurons, or SST cells, which help regulate cortical activity and behavioral flexibility. Researchers found that psilocybin increased dendritic excitability in these cells and produced lasting changes in synaptic function. In mouse experiments, those cellular effects were associated with lower motivation to pursue reward, suggesting that psychedelic action can reshape circuits involved in reinforcement and decision-making. The findings connect a specific cell type to a behavioral effect that may matter for conditions marked by maladaptive reward processing, including addiction and compulsive behavior. The work also points to a more precise biological explanation for how psilocybin can produce sustained changes after acute drug exposure.