HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ehrlichman, R. S. Articles by Siegel, S. J. PubMed Articles by Ehrlichman, R. S. Articles by Siegel, S. J.

Deviance-elicited Changes in Event-related Potentials are Attenuated by Ketamine in Mice

University of Pennsylvania

Reprint requests should be sent to Steven J. Siegel, Division of Neuropsychiatry, Stanley Center for Experimental Therapeutics in Psychiatry, Department of Psychiatry, University of Pennsylvania, Translational Research Laboratories, Rm. 2223, 125 S. 31st Street, Philadelphia, PA 19104, or via e-mail: siegels{at}mail.med.upenn.edu.

Background: People with schizophrenia exhibit reduced ability to detect change in the auditory environment, which has been linked to abnormalities in N-methyl-D-aspartate (NMDA) receptor-mediated glutamate neurotransmission. This ability to detect changes in stimulus qualities can be measured with electroencephalography using auditory event-related potentials (ERPs). For example, reductions in the N100 and mismatch negativity (MMN), in response to pitch deviance, have been proposed as endophenotypes of schizophrenia. This study examines a novel rodent model of impaired pitch deviance detection in mice using the NMDA receptor antagonist ketamine. Methods: ERPs were recorded from unanesthetized mice during a pitch deviance paradigm prior to and following ketamine administration. First, N40 amplitude was evaluated using stimuli between 4 and 10 kHz to assess the amplitude of responses across the frequency range used. The amplitude and latency of the N40 were analyzed following standard (7 kHz) and deviant (5–9 kHz) stimuli. Additionally, we examined which portions of the ERP are selectively altered by pitch deviance to define possible regions for the mouse MMN. Results: Mice displayed increased N40 amplitude that was followed by a later negative component between 50 and 75 msec in response to deviant stimuli. Both the increased N40 and the late N40 negativity were attenuated by ketamine. Ketamine increased N40 latency for both standard and deviant stimuli alike. Conclusions: The mouse N40 and a subsequent temporal region have deviance response properties similar to the human N100 and, possibly, MMN. Deviance responses were abolished by ketamine, suggesting that ketamine-induced changes in mice mimic deviance detection deficits in schizophrenia.