The cytokine erythropoietin (EPO) is an important regulator of hematopoesis and has well-known tissue protective properties. Neurotrophic action is implicated as mechanistically important in the treatment of depression, and neurotrophic actions of EPO suggest potential therapeutic utility of an EPO-like mechanism in depressive disorder. Rodent behavioral models that are responsive to clinically used antidepressants as well as to neurotrophic compounds can be used to assess potential antidepressant properties of EPO and EPO-like compounds. Rodent models described here are the forced-swim test (FST), a hyponeophagia test and the novel object recognition test. Each of these models provides different information and relevance to depression and each can be tested with EPO and similar compounds.