AAV-mediated decrease in KL protein levels increased stress susceptibility and diminished sex differences in spatial learning and memory deficit, anhedonic-like behaviors, and anxiety-like behaviors induced by 2-week CUMS. Experimental design. Sucrose preference test (SPT), open-field test (OFT), and Morris water maze (MWM) test (A). In the MWM test, CUMS did not alter the latency to the platform in KL normal rats of both sexes during 5-day training but CUMS caused a decrease in the latency to the platform in KL-KD (knockdown) rats of both sexes on day 5 during training (B). CUMS did not alter the number of platform area crossings (C) and the time spent in the target quadrant (D) in KL normal rats of both sexes. In contrast, in KL-KD rats of both sexes, CUMS decreased the number of platform area crossings (C) and the time spent in the target quadrant (D) in the MWM test. CUMS caused a decrease in sucrose consumption in the SPT (E), a decrease in the time spent in the center of the open field (F), a decrease in rearing times (G), a decrease in grooming times (H), and the total distance traveled (I) in the OFT in KL-KD rats of both sexes. Data are shown as the mean ± SEM. (B) Three-way repeated-measures ANOVA; (C–I) three-way ANOVA followed by Tukey’s test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001, n = 6–8. sh-KL, KL-shRNA; sh-Scr, control scrambled shRNA.