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    Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat

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    McLean_Behavioural_Brain_Research_2010.pdf (461.1Kb)
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    Publication date
    2010-12-25
    Author
    McLean, Samantha L.
    Neill, Joanna C.
    Idris, Nagi F.
    Marston, H.M.
    Wong, E.H.F.
    Shahid, M.
    Keyword
    Asenapine; d-Amphetamine; PCP; Reversal learning; Schizophrenia; Risperidone; Olanzapine
    Rights
    © 2010 Elsevier B.V. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
    Peer-Reviewed
    Yes
    
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    Abstract
    Background: Asenapine is a new pharmacological agent for the acute treatment of schizophrenia and bipolar disorder. It has relatively higher affinity for serotonergic and α2-adrenergic than dopaminergic D2 receptors. We evaluated the effects of asenapine, risperidone, and olanzapine on acute and subchronic psychotomimetic-induced disruption of cued reversal learning in rats. Methods: After operant training, rats were treated acutely with D-amphetamine (0.75 mg/kg intraperitoneally [i.p.]) or phencyclidine (PCP; 1.5 mg/kg i.p.) or sub-chronically with PCP (2 mg/kg i.p. for 7 days). We assessed the effects of acute coadministration of asenapine, risperidone, or olanzapine on acute D-amphetamine– and PCP-induced deficits and the effects of long-term coadministration of these agents (for 28 additional days) on the deficits induced by subchronic PCP. Results: Deficits in reversal learning induced by acute D-amphetamine were attenuated by risperidone (0.2 mg/kg i.p.). Acute PCP-induced impairment of reversal learning was attenuated by acute asenapine (0.025 mg/kg subcutaneously [s.c.]), risperidone (0.2 mg/kg i.p.), and olanzapine (1.0 mg/kg i.p.). Subchronic PCP administration induced an enduring deficit that was attenuated by acute asenapine (0.075 mg/kg s.c.) and by olanzapine (1.5 mg/kg i.p.). Asenapine (0.075 mg/kg s.c.), risperidone (0.2 mg/kg i.p.), and olanzapine (1.0 mg/kg i.p.) all showed sustained efficacy with chronic (29 d) treatment to improve subchronic PCP-induced impairments. Conclusion: These data suggest that asenapine may have beneficial effects in the treatment of cognitive symptoms in schizophrenia. However, this remains to be validated by further clinical evaluation.
    URI
    http://hdl.handle.net/10454/8465
    Version
    Accepted Manuscript
    Citation
    McLean SL, Neill JC, Idris NF, Marston HM, Wong EHF and Shahid M (2010) Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat. Behavioural Brain Research. 214(2): 240-247.
    Link to publisher’s version
    http://dx.doi.org/10.1016/j.bbr.2010.05.043
    Type
    Article
    Collections
    Life Sciences Publications

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