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Erythropoietin reverses the attentional set-shifting impairment in a rodent schizophrenia disease-like model.

Abstract：

RATIONALE:Executive function impairment, as classically assessed using the Wisconsin Card Sort Test or intradimensional/extradimensional tests, is a key feature of schizophrenia but remains inadequately treated by existing therapies. Recently, however, erythropoietin has been shown to improve attentional set-shifting performance in schizophrenic patients. OBJECTIVE:The present study utilized the rat intradimensional/extradimensional task to investigate the potential of erythropoietin to reverse a phencyclidine-induced extradimensional shift impairment when given alone or in combination with subchronic haloperidol treatment. METHODS:Rats were subjected to a subchronic systemic administration (7 days, b.i.d) of either saline vehicle or phencyclidine (5 mg/kg) followed by a 7-day washout period during which haloperidol was given. Subsequently, rats were trained to dig in baited bowls for a food reward and to discriminate on the basis of digging media or bowl odor. In experiment 1, rats performed a series of discriminations following acute administration of vehicle, erythropoietin, or modafinil. In a second experiment, rats receiving either haloperidol in the drinking water or just normal drinking water were run in the attentional set-shifting task after acute administration of erythropoietin (1,000 or 10,000 IU/ml i.p., selected from experiment 1). RESULTS:The subchronic phencyclidine-induced extradimensional deficit was ameliorated by both erythropoietin and modafinil. When combined with subchronic haloperidol, the higher dose of erythropoietin tested was able to reverse the extradimensional shift impairment. CONCLUSIONS:Overall, these findings further support the use of erythropoietin as an adjunct to antipsychotic therapy in order to address, at least part of, the cognitive dysfunction associated with schizophrenia.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Goetghebeur PJ,Lerdrup L,Sylvest A,Dias R

doi

10.1007/s00213-010-1990-9

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

635-42

issue

eissn

0033-3158

issn

1432-2072

journal_volume

212

pub_type

杂志文章

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Erythropoietin reverses the attentional set-shifting impairment in a rodent schizophrenia disease-like model.