Objective To investigate the roles of estrogen and kalirin-7 in chronic restraint stress （CRS）-induced depression and the pathophysiological mechanism of depression. Methods Healthy female mice from Institute of Cancer Research （ICR） were randomly divided into 3 groups： control group, CRS group, and estrogen ＋ CRS group. CRS was used to establish the animal model of depression. Forced swimming test and immunohistochemistry method were utilized to investigate the animal behavior and kalirin-7 expression in the hippocampus, respectively. Results Compared with the control group, the CRS mice displayed depression-like behaviors, including a significant reduction in body weight, a significant increase in immobility time in forced swimming test, and a dramatic decrease in kalirin-7 expression in the hippocampus. However, administration of estrogen attenuated the CRS-induced negative behaviors, and simultaneously increased kalirin-7 expression. Conclusion Estrogen replacement therapy （ERT） could prevent CRS-induced depression-like behaviors in female ICR mice. Besides, kalirin-7 also plays a role in preventing CRS-induced depression-like behaviors.
