Erythropoietin improves operant conditioning and stability of cognitive performance in mice
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BioMed Central
Open Access
Research article
Erythropoietin improves operant conditioning and stability of cognitive performance in mice Ahmed El-Kordi†, Konstantin Radyushkin† and Hannelore Ehrenreich* Address: Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany Email: Ahmed El-Kordi - [email protected]; Konstantin Radyushkin - [email protected]; Hannelore Ehrenreich* - [email protected] * Corresponding author †Equal contributors
Published: 8 July 2009 BMC Biology 2009, 7:37
doi:10.1186/1741-7007-7-37
Received: 6 February 2009 Accepted: 8 July 2009
This article is available from: http://www.biomedcentral.com/1741-7007/7/37 © 2009 El-Kordi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion. Results: Male mice were treated for 3 weeks with erythropoietin (5,000 IU/kg) versus placebo intraperitoneally every other day, beginning at postnatal day 28. After termination of treatment, mice were started on the Five Choice Serial Reaction Time Task, with daily training and testing extending to about 3 months. Overall, a significantly higher proportion of erythropoietin-treated mice finished the task, that is, reached the criteria of adequately reacting to a 1.0 sec flash light out of five arbitrarily appearing choices. During acquisition of this capability, that is, over almost all sequential training phases, learning readouts (magazine training, operant and discriminant learning, stability of performance) were superior in erythropoietin-treated versus control mice. Conclusion: Early erythropoietin treatment leads to lasting improvement of cognitive performance in healthy mice. This finding should be exploited in novel treatment strategies for brain diseases.
Background The haematopoietic growth factor erythropoietin (EPO) has been in clinical use for over 20 years to treat patients with anaemic conditions, ranging from renal failure to cancer. Upon introduction of EPO to the clinic, it was
observed that cognitive performance of treated individuals also improved. This improvement was esse
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