RAC1 and major depressive disorder: However, contrary to our findings that ketamine treatment reduces chronic pain–induced depressive-like behaviors by blocking increases in Tiam1-Rac1 activation, dendritic spine density, and synaptic NMDAR levels and function in the ACC, ketamine was shown to improve depression-like behaviors in stressed rats by upregulating Rac1 activity and increasing dendritic spine density and synaptic-related protein expression in the hippocampus (58).