Appetite for change: How psilocybin reshapes food reward learning through striatal dopamine function
bioRxiv May 18, 2026 Kyna Conn, Ngok Wong, Serenay Sunnetci et al.
A single dose of psilocybin (1.5 mg/kg) in female rats enhanced cognitive flexibility in several learning tasks by amplifying dopamine signals in the nucleus accumbens. The drug increased learning rates and reduced reliance on prior expectations, leading to faster reversal learning. However, calorie restriction and prior exposure to activity-based anorexia (ABA) reduced these benefits. Calorie restriction shifted the timing of psilocybin's effect on reversal learning and increased neural activity in the nucleus accumbens. Prior ABA exposure eliminated improvements in discrimination accuracy and trended toward worsening reversal learning, likely due to reduced cortical 5-HT2A receptor availability. The results show that nutritional state and history of anorexia-like behavior critically moderate psilocybin's cognitive effects.