Intranasal and intra-mPFC injections of RvE1 produce antidepressant-like actions via mTORC1 activation in the mPFC in LPS-induced depression model mice. a Experimental timeline for LPS challenge (0.8 mg/kg, i.p.), intra-mPFC infusion of either vehicle 1 (10% DMSO/PBS) or rapamycin (0.01 nmol/side), i.n. administration of either vehicle 2 (0.5% ethanol/PBS) or RvE1 (10 ng/mouse), and behavioral testing. b Effects of intra-mPFC infusion of rapamycin and i.n. administration of RvE1 on LMA in LPS-challenged mice (interaction, F1,16 = 0.0379, p = 0.848; rapamycin, F1,16 = 2.87, p = 0.110; RvE1, F1,16 = 2.09, p = 0.167). c, d Effects of intra-mPFC infusion of rapamycin on the antidepressant-like actions of i.n. administration of RvE1 in the TST (c, interaction, F1,16 = 12.8, p = 0.0025) and FST (d, interaction, F1,16 = 7.16, p = 0.0165) in LPS-challenged mice. e Schematic representation of the mPFC infusion sites. Plates are from ref. 36. f Experimental timeline for LPS challenge, intra-mPFC infusion of vehicle (10% DMSO/0.25% ethanol/PBS), RvE1 (50 pg/side) or RvE1 + rapamycin (0.01 nmol/side), and behavioral testing. g–i Effects of intra-mPFC infusion of RvE1 with or without rapamycin on LMA (g, one-way ANOVA, F2,16 = 0.761, p = 0.483) and immobility time in the TST (h, one-way ANOVA, F2,16 = 7.33, p = 0.0055) and FST (i, one-way ANOVA, F2,16 = 22.2, p < 0.0001) in LPS-challenged mice. j Schematic representation of the mPFC infusion sites. Plates are from ref. 36. Data are expressed as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 [two-way ANOVA (b–d) and one-way ANOVA (g–i) followed by Holm-Sidak’s post hoc test]