Previous research has shown that fibroblast growth factor 2 protein (FGF2) can act as an anxiolytic and anti-depressive agent in rodents. Hippocampal FGF2 are decreased in post-mortem brains of individuals with mood disorders. No changes in FGF2 noted in the post-mortem brains of individuals with mood disorders that were successfully treated with anti-depressant medication. Mutations in FGF2 gene in humans have predicted non-responsiveness to the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs). These findings suggest FGF2 may be required for the therapeutic effects of antidepressants. To test this, we employed a rodent model of depressive behaviour, chronic variable stress (CVS) with antidepressant treatment (fluoxetine) in wild-type and FGF2 knockout mice and examined depressive and anxiety behaviors. We hypothesized that fluoxetine will reverse the effects of CVS on these behaviours in wild-type mice, but not in FGF2KO, suggesting that FGF2 gene is necessary for the therapeutic effects of fluoxetine.