Acetylsalicylic acid as an augmentation agent in fluoxetine treatment resistant depressive rats

Clinical studies have reported that adjunctive acetylsalicylic acid (aspirin) therapy is beneficial for patients with treatment resistant depression (TRD). However, there still exist negative epidemiological data on the link between aspirin and depression. Therefore, this study aimed to further investigate whether aspirin can be used as an augmentation agent in fluoxetine treatment resistant depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and antidepressant treatment were assessed by behavioral testing, hippocampal expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). 4-week fluoxetine treatment reversed the behavioral changes in approximately 70-80% depressive rats. That is, 20-30% depressive rats were resistant to fluoxetine. In the hippocampus of fluoxetine treatment resistant depressive rats, a significant upregulation of COX-2 level and PGE(2) concentration was observed. However, in these rats adjunctive aspirin treatment significantly improved the depressive behaviors and downregulated the COX-2 level and PGE(2) concentration in the hippocampus. Thus, our results suggest that aspirin can be served as an effective adjunctive agent in the treatment resistant depression mediated by inhibition of the COX-2 level and PGE(2) concentration.