Psilocybin Decreases Preference for Large Rewards Accompanied by Increased Activity of Parvalbumin Neurons With Perineuronal Nets in the Medial Prefrontal Cortex.
The European journal of neuroscience June 1, 2026 Jenna Houff, Andrew Williams, Obie Allen et al.
A single dose of psilocybin reduced choices for larger, delayed rewards and increased the time rats took to choose them, measured 48 hours after administration. This effect was not tied to the delay length, indicating it did not alter impulsivity. Instead, the pattern suggests psilocybin decreased motivation for rewards. In the dorsomedial prefrontal cortex, psilocybin increased the density of neurons that were positive for perineuronal nets, parvalbumin, and c-Fos, pointing to heightened activity of a specific class of inhibitory interneurons. These findings propose that psilocybin lowers appetitive motivation by activating parvalbumin-positive interneurons surrounded by perineuronal nets in this brain region.