Behavioral response to fluoxetine in both female and male mice is modulated by dentate gyrus granule cell activity.

Depression is a complex psychiatric disorder that is a major burden on society, with only ~33% of depressed patients attaining remission upon initial monotherapy with a selective serotonin reuptake inhibitor (SSRI). In preclinical studies using rodents, chronic stress paradigms, such as chronic corticosterone and social instability stress, are used to induce avoidance behaviors associated with negative affective states. Chronic fluoxetine (FLX; an SSRI) treatment reverses these chronic stress-induced behavioral changes in some, but not all mice, permitting stratification of mice into behavioral responders and non-responders to FLX.

Chronic non-discriminatory social defeat is an effective chronic stress paradigm for both male and female mice.

Stress-related mood disorders are more prevalent in females than males, yet preclinical chronic stress paradigms were developed in male rodents and are less effective in female rodents. Here we characterize a novel chronic non-discriminatory social defeat stress (CNSDS) paradigm that results in comparable stress effects in both sexes. Male and female C57BL/6J mice were simultaneously introduced into the home cage of resident CD-1 aggressors for 10 daily 5-min sessions.