The neurotrophic hypothesis of depression has focused on the role of BDNF in hippocampus in the pathophysiology and treatment of depression. The CaMKII-Cre × flBDNF mice have residual expression of BDNF in hippocampus, yet both this line and the GFAP-Cre driven BDNF KO line show similar gender differences in depression-related behaviors. These data suggest that even a partial loss of BDNF in hippocampus may be sufficient to mediate depression-related behavior in female mice.