a, b Intra-NAc infusion of Ro 25–6981 (0.1 μM, 0.5 μl) 20 min before test did not affect the time in interaction zone and social interaction ratios (a) and sucrose preference (b) in susceptible mice, while it obviously abolished the enhancement effect of klotho overexpression on time in interaction zone and social interaction ratios (a) and sucrose preference (b) in these mice (n = 10 mice per group). c–g NMDAR-dependent LTD recorded in the NAc in control (c), Sus + GFP (d), Sus + GFP + Ro-25 (e), Sus + KL-OE (f) and Sus + KL-OE + Ro-25 group (g). Bath application of Ro 25–6981 (0.1 μM) for 20 min did not affect LFS-induced NMDAR-dependent LTD in slices from susceptible mice, but clearly abolished the beneficial effects of klotho overexpression on LTD in these mice. h The box and whiskers show the level of normalized fEPSP slope 40 min after LFS from each group (n = 6 per group). For (a–d) and (j), all box and whisker plot display the median, first and third quartiles (boxes), and the min-max (whiskers), and other data were presented as normalized mean ± SEM. **p < 0.01 vs. control; ##p < 0.01 vs. Sus + GFP group; &&p < 0.01 vs. Sus + KL-OE group.