alexa A Possible Mechanism of Antidepressant like Effect of R
ISSN: 2155-9562

Journal of Neurology & Neurophysiology
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Research Article

A Possible Mechanism of Antidepressant like Effect of Recombinant Human Erythropoietin

Pawar AS1, Barve KH1*, Patel A2, Raje A3 and Addepalli VA1

1Shobhaben Pratapbhai Patel-School of Pharmacy and Technology Management, SVKM’s NMIMS, Mumbai, Maharashtra, India

2Wockhardt Research Centre, D-4 Chikalthana, Aurangabad, Dist. Aurangabad, Maharashtra, India

3Vimta Labs Ltd., Nallagutta, Secunderabad, Andhra Pradesh, India

Corresponding Author:
Kalyani Barve
SPP-School of pharmacy and technology management
5th floor mithibai college building
V.L. Mehta road, Vile Parle, Mumbai 400056, India
Tel: 9920467646
Fax: 91-22-26185422
E-mail: [email protected]

Received date: July 18, 2014; Accepted dat: August 13, 2014; Published date: August 20, 2014

Citation: Pawar AS, Barve KH, Patel A, Raje A, Addepalli VA (2014) A Possible Mechanism of Antidepressant like Effect of Recombinant Human Erythropoietin. J Neurol Neurophysiol 5:222. doi:10.4172/2155-9562-5-1000222

Copyright: © 2014 Barve KH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



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.


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