Psilocybin dampens rats’ reward pursuit by activating prefrontal inhibitory neurons

A rat study found that a single psilocybin dose (1 mg/kg, given intraperitoneally) reduced the rats’ preference for larger rewards 48 hours after administration, by increasing activity of parvalbumin inhibitory interneurons wrapped in perineuronal nets in the medial prefrontal cortex. This linked change in brain circuitry suggests psilocybin may dampen incentive motivation and alter reward processing, offering insight into potential mechanisms for treating substance-use disorders. Results are preliminary and limited to male rats, with no impairment to attention or basic motor skills observed.