Biology Reference
In-Depth Information
Chapter 8
Evaluating Effects of EPO in Rodent Behavioral Assays
Related to Depression
Catharine H. Duman and Samuel S. Newton
Abstract
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 mecha-
nism 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 rele-
vance to depression and each can be tested with EPO and similar compounds.
Key words
EPO, CEPO, Depression, Behavior, Swim test, Object recognition, Hyponeophagia
1
Introduction
Erythropoietin (EPO) is widely recognized for its role in elevating
erythropoiesis and is used successfully to treat anemia. EPO recep-
tors are expressed in neuronal cell lines and in brain, and in addi-
tion to its hematopoietic effects in the periphery, EPO can exert
neurotrophic and angiogenic effects in the central nervous system
(
1-5
).
A neuroprotective action of EPO suggests a variety of thera-
peutic applications but such applications could be limited by the
erythropoietic effect during long-term administration. The separa-
tion of erythropoietic from neuroprotective mechanisms has been
investigated based on specificity of receptor complexes and signal-
ing pathways that mediate neuroprotection vs. hematopoiesis, and
EPO derivatives have been developed that do not increase hemat-
ocrit but retain tissue protective properties (
5-7
). Non-
erythropoietic EPO-like compounds can be tested in research
1.1 Erythropoietin,
Neuroprotection,
and Depression
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