title: Late deviance detection in rats is reduced, while early deviance detection is augmented by the NMDA receptor antagonist MK-801.
abstract: One of the most robust electrophysiological features of schizophrenia is reduced mismatch negativity, a component of the event related potential (ERP) induced by rare and unexpected stimuli in an otherwise regular pattern. Emerging evidence suggests that mismatch negativity (MMN) is not the only ERP index of deviance detection in the mammalian brain and that sensitivity to deviant sounds in a regular background can be observed at earlier latencies in both the human and rodent brain. Pharmacological studies in humans and rodents have previously found that MMN reductions similar to those seen in schizophrenia can be elicited by N-methyl-d-aspartate (NMDA) receptor antagonism, an observation in agreement with the hypothesised role of NMDA receptor hypofunction in schizophrenia pathogenesis. However, it is not known how NMDA receptor antagonism affects early deviance detection responses. Here, we show that NMDA antagonism impacts both early and late deviance detection responses. By recording EEG in awake, freely-moving rats in a drug-free condition and after varying doses of NMDA receptor antagonist MK-801, we found the hypothesised reduction of deviance detection for a late, negative potential (N55). However, the amplitude of an early component, P13, as well as deviance detection evident in the same component, were increased by NMDA receptor antagonism. These findings indicate that late deviance detection in rats is similar to human MMN, but the surprising effect of MK-801 in increasing ERP amplitudes as well as deviance detection at earlier latencies suggests that future studies in humans should examine ERPs over early latencies in schizophrenia and after NMDA antagonism.
authors.affiliation: School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; Schizophrenia Research Institute, Randwick, NSW, Australia. Electronic address: lauren.harms@newcastle.edu.au.
authors.forename: L
authors.initials: L
authors.lastname: Harms
authors.affiliation: School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: W R
authors.initials: WR
authors.lastname: Fulham
authors.affiliation: Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Todd
authors.affiliation: School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Meehan
authors.affiliation: Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; Schizophrenia Research Institute, Randwick, NSW, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: U
authors.initials: U
authors.lastname: Schall
authors.affiliation: School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; Schizophrenia Research Institute, Randwick, NSW, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Hodgson
authors.affiliation: School of Psychology, University of Newcastle, Callaghan, NSW, Australia; Priority Centre for Brain and Mental Health Research, Callaghan, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia; Schizophrenia Research Institute, Randwick, NSW, Australia.
authors.forename: P T
authors.initials: PT
authors.lastname: Michie
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D003265:Contingent Negative Variation / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
keywords: MK-801; Mismatch negativity (MMN); N-methyl-d-aspartate (NMDA) receptor; Predictive coding; Rat; Schizophrenia