Intranasal administration of RvE1 produces antidepressant-like actions via mTORC1 activation in the mPFC in repeated PSL-induced depression model mice. a Experimental timeline for PSL treatment (50 mg/kg, s.c., once a day for 6 days), i.n. administration of either vehicle (0.5% ethanol/PBS) or RvE1 (10 ng/mouse), and behavioral testing. b, c Effects of PSL and RvE1 on total distance traveled (b, interaction, F1,56 = 0.0793, p = 0.779; PSL, F1,56 = 0.829, p = 0.366; RvE1, F1,56 = 0.326, p = 0.570) and time in center (c, interaction, F1,56 = 0.0605, p = 0.807; PSL, F1,56 = 1.38, p = 0.245; RvE1, F1,56 = 4.37, p = 0.0411) in the OFT. d Effects of PSL and RvE1 on immobility time in the FST (interaction, F1,56 = 6.36, p = 0.0146). e Experimental timeline for PSL treatment (50 mg/kg, s.c., once a day for 6 days), 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 (f, g) Effects of intra-mPFC infusion of rapamycin and i.n. administration of RvE1 on total distance traveled (f, interaction, F1,21 = 4.85, p = 0.039) and time in center (g, interaction, F1,21 = 0.0710, p = 0.793; rapamycin, F1,21 = 1.05, p = 0.318; RvE1, F1,21 = 0.978, p = 0.334) in the OFT in PSL-treated mice. h Effects of intra-mPFC infusion of rapamycin on the antidepressant-like actions of i.n. administration of RvE1 in the FST (interaction, F1,21 = 4.76, p = 0.0407). i Schematic representation of the mPFC infusion sites. Plates are from ref. 36. Data are expressed as mean ± SEM. *p < 0.05, **p < 0.01 (two-way ANOVA followed by Holm-Sidak’s post hoc test)