Fig. 1: 5HT2AR and 5HT1AR antagonism does not block the beneficial effects of psilocybin on novel object discrimination in Fmr1-^Δexon 8 rats.

Systemic administration of the 5HT2AR selective antagonist M100 (0.25 mg/kg, i.p.) did not counteract the positive effects of psilocybin (PSY) on object recognition in Fmr1-^Δexon 8 rats (A). Total object exploration time during testing was unaffected by treatment across genotypes (B) (WT-VEH/VEH = 8, WT-VEH/PSY = 9, WT-M100/VEH = 9, WT-M100/PSY = 10, Fmr1-^Δexon 8-VEH/VEH = 10, Fmr1-^Δexon 8- VEH/PSY = 9, Fmr1-^Δexon 8- M100/VEH = 10, Fmr1-^Δexon 8-M100/PSY = 9). Similarly, administration of the 5HT1AR selective antagonist WAY (0.3 mg/kg, i.p.) failed to prevent the recognition memory-enhancing effects of psilocybin in Fmr1- ^Δexon 8 rats (C), and had no impact on total object exploration time (D) (WT-VEH/VEH = 9, WT-VEH/PSY = 10, WT-WAY/VEH = 6, WT-WAY/PSY = 9, Fmr1-^Δexon 8-VEH/VEH = 8, Fmr1-^Δexon 8- VEH/PSY = 8, Fmr1-^Δexon 8- WAY/VEH = 7, Fmr1-^Δexon 8-WAY/PSY = 10). Data represent mean ± SEM, ^**p < 0.01, ^***p < 0.001 vs WT-VEH/VEH group, ^#p < 0.05, ^##p < 0.01, vs Fmr1-^Δexon 8-VEH/VEH group; (three-way ANOVA followed by Tukey’s post hoc test).