Figure 5.

Pharmacological inhibition of HDAC4/5 induces antidepressant-like behaviors. A, Structure of LMK-235, a selective HDAC4/5 inhibitor. B, Schematic of the experimental design to show that HDAC4/5 inhibition reduces depression-like behaviors. BALB/c mice were continuously infused with LMK-235 or vehicle into the bilateral hippocampus using osmotic minipumps. Two weeks after pump implantation, mice were tested using behavioral assays. C, Location of the cannula tips. D–G, Behavioral results. D, SI time in the SI. E, Immobility time in the FST. F, Latency to feeding in the NSF. G, Sucrose preference in the SPT. n = 10–12 mice per group. LMK-235 enhanced SI (D) and reduced both immobility time (E) and latency to feeding (F). *p < 0.05 versus vehicle control. H, Schematic of the experimental design to demonstrate that HDAC4/5 inhibition reduces depression-like behaviors in stressed mice. BALB/c mice were infused with LMK-235 or vehicle into the hippocampus using osmotic minipumps. One week after pump implantation surgery, mice were subjected to severe RRS (4 h/d) for 10 d. The mice were then tested using behavioral assays. I, Location of the cannula tips. J, K, Behavioral results. J, SI time in the SI. K, Sucrose preference in the SPT. n = 11–14 per group. *p < 0.05 versus NS mice receiving vehicle. All data are presented as mean ± SEM.