Behavioural sensitisation to MK-801 is dose-dependent and independent of environmental context

Lefevre, Emilia M., Eyles, Darryl W. and Burne, Thomas H. J. (2016) Behavioural sensitisation to MK-801 is dose-dependent and independent of environmental context. Behavioural Brain Research, 298 Part B: 241-245. doi:10.1016/j.bbr.2015.11.014

Author Lefevre, Emilia M.
Eyles, Darryl W.
Burne, Thomas H. J.
Title Behavioural sensitisation to MK-801 is dose-dependent and independent of environmental context
Journal name Behavioural Brain Research   Check publisher's open access policy
ISSN 1872-7549
Publication date 2016-02-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.bbr.2015.11.014
Open Access Status Not Open Access
Volume 298
Issue Part B
Start page 241
End page 245
Total pages 5
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2016
Language eng
Abstract The pathophysiology of schizophrenia is associated with disturbed glutamate signalling, particularly via a dysfunction of the N-methyl- d-aspartate (NMDA) receptor. In rodents, behavioural sensitisation to the NMDA receptor antagonist MK-801 is proposed to recapitulate aspects of the NMDA receptor hypofunction hypothesis of schizophrenia. The aim of this study was to determine the modulatory role of MK-801 dose and environmental context on the development and expression of MK-801-induced behavioural sensitisation. Sprague Dawley rats were administered saline or varying doses of MK-801 (i.p.) once daily for 7 days and locomotor activity was recorded. After 5 days of withdrawal, rats were challenged with their respective dose to test for sensitisation. From this experiment a sensitising dose was obtained. In the second experiment the magnitude of sensitisation was compared between rats that were treated in either a home or test environmental context. Rats treated with 0.25. mg/kg MK-801 developed robust sensitisation when challenged after withdrawal. Rats treated with lower (0.1. mg/kg) or higher (0.5. mg/kg) doses of MK-801 did not develop locomotor sensitisation. Sensitisation to 0.25. mg/kg MK-801 developed equally between rats treated in the home or test context. The study shows that male Sprague Dawley rats develop behavioural sensitisation to repeated injections of MK-801. The development of sensitisation is selective to MK-801 dose in an inverted-U dose response fashion. In this paradigm MK-801 induced sensitisation was expressed similarly between groups treated in two distinct environmental contexts.
Keyword Animal model
Environmental context
NMDA receptor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
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