Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin
View/ Open
Issue Date
2013-06Author
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
Metadata
Show full item recordAbstract
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
ISSN
1461-1457Collections
- Pharmacy Scholarly Works [293]
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
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.