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Translational Aspects of the Novel Object Recognition Task in Rats Abstinent Following Sub-Chronic Treatment with Phencyclidine (PCP): Effects of Modafinil and Relevance to Cognitive Deficits in Schizophrenia

Authors: Redrobe, John P.; Bull, Sascha; Plath, Niels;

Translational Aspects of the Novel Object Recognition Task in Rats Abstinent Following Sub-Chronic Treatment with Phencyclidine (PCP): Effects of Modafinil and Relevance to Cognitive Deficits in Schizophrenia

Abstract

Phencyclidine (PCP) induces a behavioral syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS) has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR) task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p.) or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP treatment. Acute treatment with modafinil (64 mg/kg, p.o.) ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c.), risperidone (0.2 mg/kg, i.p.), and donepezil (3 mg/kg, p.o.) were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.

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Keywords

cognition, Psychiatry, Novel object recognition, RC435-571, Phencyclidine, phencyclidine, Modafinil, schizophrenia, Cognition, novel object recognition, Schizophrenia, rat, modafinil

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
32
Top 10%
Top 10%
Top 10%
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