title: Behavioural sensitisation to MK-801 is dose-dependent and independent of environmental context.
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 0.25mg/kg MK-801 developed robust sensitisation when challenged after withdrawal. Rats treated with lower (0.1mg/kg) or higher (0.5mg/kg) doses of MK-801 did not develop locomotor sensitisation. Sensitisation to 0.25mg/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.
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Emilia M
authors.initials: EM
authors.lastname: Lefevre
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, QLD 4076, Australia.
authors.forename: Darryl W
authors.initials: DW
authors.lastname: Eyles
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, QLD 4076, Australia. Electronic address: t.burne@uq.edu.au.
authors.forename: Thomas H J
authors.initials: TH
authors.lastname: Burne
mesh_terms: D056044:Actigraphy; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D006799:Housing, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012984:Software; D014741:Video Recording
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: Animal model; Environmental context; MK-801; NMDA receptor; Schizophrenia; Sensitisation