(A) Schematic depicting the experimental design. A SPT was performed on Day 1 followed by 10 days of chronic CORT administration. A second SPT was performed on Day 12 prior to administration of VEH or PSY (10 mg/kg, IP) on Day 13. On day 14, a third SPT was performed. (B) Chronic administration of CORT induced anhedonia in both WT and 5-HT2AR KO mice. (C) A single administration of PSY rescued CORT-induced anhedonia in WT, but not 5-HT2AR KO mice. Administration of VEH had no effect in either genotype. VEH = vehicle; PSY = psilocybin; WT = wild type. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, Student’s t-test (paired).