CUS‐induced behavioral despair, cognitive impairment, and neuroinflammation are prevented by RAGE knockdown. (A) Schematic depicting experimental approach and timeline. Male wild‐type mice received bilateral infusion of AAV2sh−NC or AAV2sh−RAGE and were subjected to 14 days of CUS. (B‐E) Immobility in the FST, total sucrose consumer, latency to feed in the NSF, and discrimination index in the TOR were shown (n = 8 per group). (F) The protein levels of RAGE and FBXO10 in PFC were detected by Western blotting (n = 3 per group). (G) The levels of TNF‐α, IL‐1β, IL‐6, IL‐10, TGF‐β, and BDNF in tissue homogenate of medial PFC were measured using ELISA (n = 3 per group). Bars represent the mean ±SEM. *P < 0.05, *P < 0.01 vs. AAV2sh−NC control mice; &P < 0.05 vs. AAV2sh−NC CUS mice