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Late deviance detection in rats is reduced, while early deviance detection is augmented by the NMDA receptor antagonist MK-801

journal contribution
posted on 2023-05-19, 18:42 authored by Harms, L, Fulham, WR, Todd, J, Crystal MeehanCrystal Meehan, Schall, U, Hodgson, DM, Michie, PT
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.

History

Publication title

Schizophrenia research

Volume

191

Pagination

43-50

ISSN

0920-9964

Department/School

School of Psychological Sciences

Publisher

Elsevier Science Bv

Place of publication

Po Box 211, Amsterdam, Netherlands, 1000 Ae

Rights statement

© 2017 Elsevier B.V. All rights reserved.

Repository Status

  • Restricted

Socio-economic Objectives

Mental health

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