Pawar AS, Barve KH, Patel A, Raje A and Addepalli VA
Objective: Recombinant human erythropoietin is clinically proved to have antidepressant like effect. The present
study deals with evaluating the possible mechanism of action of the antidepressant effect of recombinant human
Methods: The antidepressant activity of subcutaneously administered rH-Epo was tested in models of acute
stress and chronic stress. Simultaneous administration of rH-Epo in sub-effective dose with sub-therapeutic doses of
standard anti-depressants/agonist and antagonist of various receptors was done in mice to study the potential
mechanism of antidepressant effect of rH-Epo using the tail suspension test. One-way or two-way ANOVA, followed
by post- Turkey test and Paired T test were applied wherever appropriate.
Results: In acute stress model, rH-Epo produced significant decrease in immobility period in the dose range of
500 - 4000 IU/kg comparable to standard antidepressant. However dose dependency was not observed. In chronic
stress model, animals receiving stress showed significant decrease in rotarod activity, while pre-treated animals with
rH-Epo showed improvement in rotarod activity. rH-Epo at sub-effective dose, when combined with sub-therapeutic
doses of standard anti-depressants showed significant potentiation of antidepressant action. Antidepressant effect of
rH-Epo was completely blocked by therapeutic dose of Pindolol and Haloperidol, whereas clonidine partially blocked
it. Animals, pre-treated with sub-therapeutic dose of rH-Epo when injected with Yohimbine, showed moderate
potentiation of response.
Conclusion: Reversal of chronic stress induced depressive symptoms by rH-Epo treatment is indication of
upregulation of serotonergic receptors. There might be involvement of serotonergic and adrenergic system in
antidepressant effect of rH-Epo.