Pharmacological inhibition of GSK3 induces antidepressant-like behaviors. A, Structure of LY2090314, a selective GSK3 inhibitor. B, Schematic of the experimental design to show that GSK3 inhibition suppresses depression-like behaviors. BALB/c mice were bilaterally infused with LY2090314 or vehicle into the hippocampus using osmotic minipumps. Two weeks after pump implantation surgery, mice were tested using behavioral assays. C, The 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. Inhibition of GSK3 increased SI (D) and reduced latency to feeding (F). *p < 0.05 versus vehicle control. H, Schematic of the experimental design to show that GSK3 inhibition suppresses depression-like behaviors in stressed mice. BALB/c mice were infused with LY2090314 or vehicle into the bilateral hippocampus using osmotic minipumps. One week after pump implantation surgery, mice were subjected to severe RRS (4 h/d) for 10 d and 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 = 12–15 per group. *p < 0.05 versus NS mice receiving vehicle. All data are presented as mean ± SEM.