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
erythropoietin (rH-Epo).
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.