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    Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin

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    Bortolato_et_al_June2013.pdf (446.3Kb)
    Issue Date
    2013-06
    Author
    Bortolato, Marco
    Yardley, Megan M.
    Khoja, Sheraz
    Godar, Sean C.
    Asatryan, Liana
    Finn, Deborah A.
    Alkana, Ronald L.
    Louie, Stan G.
    Davies, Daryl
    Publisher
    Cambridge University Press
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate. In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioural functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioural organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviours in the tail-suspension and forced swim tests. The agent induced no significant behavioural changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by pre-pulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gating
    Description
    This is the publisher's version, also available electronically from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8920271&fileId=S1461145712000909
    URI
    http://hdl.handle.net/1808/14791
    DOI
    https://doi.org/10.1017/S1461145712000909
    ISSN
    1461-1457
    Collections
    • Pharmacy Scholarly Works [259]
    Citation
    Bortolato Marco et al. (2013). Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin. The International Journal of Neuropsychopharmacology 16(5):1059-1070. http://dx.doi.org/10.1017/S1461145712000909

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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