The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components.
N-methyl-D-aspartate (NMDA) antagonists produce behavioral and electrophysiological effects similar to schizophrenia. The mouse P20, N40, and P80 event related potential (ERP) components were analyzed for genetic variance among inbred strains and ketamine-induced differences to model abnormalities in the P50, N100, and P200 in schizophrenia. Ketamine increased P20/N40 amplitude and decreased P80 amplitude. Therefore, the effects of ketamine in mice are inconsistent with alterations in the corresponding P50 and N100 in schizophrenia, suggesting that NMDA receptor dysfunction may not underlie abnormalities of these components in schizophrenia. However, the effects of ketamine on the mouse P80 were consistent with P200 ERP changes in schizophrenia and support the hypothesis that NMDA dysfunction may contribute to some neuronal abnormalities in schizophrenia. The current study lays the groundwork for defining the role of NMDA-mediated transmission for specific aspects of neuronal processing that vary with genetic background. Future studies could use transcription profiling to clarify such interactions between genetic background, specific neuronal circuits, and transmitter systems.
Connolly
Patrick M
PM
Stanley Center for Experimental Therapeutics, Division of Neuropsychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Maxwell
Christina
C
Liang
Yuling
Y
Kahn
Jonathan B
JB
Kanes
Stephen J
SJ
Abel
Ted
T
Gur
Raquel E
RE
Turetsky
Bruce I
BI
Siegel
Steven J
SJ
D000818:Animals; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology*; D013045:Species Specificity
D016202:N-Methylaspartate; D007649:Ketamine