Erythropoietin improves operant conditioning and stability of cognitive performance in mice.
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.


CONCLUSIONS
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.
El-Kordi
Ahmed
A
Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. kordi@em.mpg.de
Radyushkin
Konstantin
K
Ehrenreich
Hannelore
H
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007274:Injections, Intraperitoneal; D053208:Kaplan-Meier Estimate; D007858:Learning / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D015983:Selection Bias; D013647:Task Performance and Analysis
D004921:Erythropoietin