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. 2022 Jan 1;12(2):603–619. doi: 10.7150/thno.67410

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HDAC6 inhibition with ACY-1083 reverses doxorubicin-induced deficits in executive functioning, working and spatial memory. (A) Female mice were intraperitoneally treated with doxorubicin (5mg/kg) or PBS, followed by 14 daily administrations of ACY-1083 (10mg/kg) or vehicle. Cognitive function was tested 4 weeks after the final dose of ACY-1083. (B) Performance in the puzzle box test with 3 levels of complexity: An open tunnel (easy trials 1-4), a bedding-covered tunnel (intermediate trials 5-7), and a cardboard-plugged tunnel (difficult trials 8-11). Time taken to enter the goal box is recorded. (C) The average time taken to enter the goal box during the cardboard-plugged trials (difficult trials 8-11). (D) Performance in the NOPRT. The time mice spent interacting with each object was tracked. The discrimination index was calculated as (T_Novel - T_Familiar) / (T_Novel + T_Familiar). Results are expressed as mean ± SEM; n = 8-16 mice/group; Two-way ANOVA with Tukey's post hoc analysis *p ≤ 0.05; **p ≤ 0.01; **** p ≤ 0.0001.