Major depressive disorder is among the leading causes of disability worldwide, with an estimated 350 million people affected. Using transgenic mice that express green fluorescent protein in astroglial cells, we employed a chronic unpredictable stress paradigm in conjunction with chronic administration of the selective serotonin reuptake inhibitor, fluoxetine, as an antidepressant treatment. Changes in behaviour and in cortical astroglia were examined using a variety of techniques across all groups. As expected, CUS significantly increased anxiety and depressive-like behaviours, however ADT did not reverse the effects, and, in some cases exacerbated the effect of stress. Using immunohistochemistry to examine the brains we found that total number of astroglial cells (as marked by constitutive astroglial-specific GFP) in the cortex did not change in response to stress or treatment, but their expression of intermediate filament proteins did. Future studies will examine the causal involvement of differentially expressed pathways in response to stress.