PMID- 19015010
OWN - NLM
STAT- MEDLINE
DCOM- 20090415
LR  - 20220227
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 158
IP  - 2
DP  - 2009 Jan 23
TI  - N-methyl-d-aspartic acid receptor antagonist-induced frequency oscillations in 
      mice recreate pattern of electrophysiological deficits in schizophrenia.
PG  - 705-12
LID - 10.1016/j.neuroscience.2008.10.031 [doi]
AB  - INTRODUCTION: Electrophysiological responses to auditory stimuli have provided a 
      useful means of elucidating mechanisms and evaluating treatments in psychiatric 
      disorders. Deficits in gating during paired-click tasks and lack of mismatch 
      negativity following deviant stimuli have been well characterized in patients 
      with schizophrenia. Recently, analyses of basal, induced, and evoked frequency 
      oscillations have gained support as additional measures of cognitive processing 
      in patients and animal models. The purpose of this study is to examine frequency 
      oscillations in mice across the theta (4-7.5 Hz) and gamma (31-61 Hz) bands in 
      the context of N-methyl-d-aspartic acid receptor (NMDAR) hypofunction and 
      dopaminergic hyperactivity, both of which are thought to serve as pharmacological 
      models of schizophrenia. EXPERIMENTAL PROCEDURES: Electroencephalograms (EEG) 
      were recorded from mice in five treatment groups that consisted of haloperidol, 
      risperidone, amphetamine, ketamine, or ketamine plus haloperidol during an 
      auditory task. Basal, induced and evoked powers in both frequencies were 
      calculated. RESULTS: Ketamine increased basal power in the gamma band and 
      decreased the evoked power in the theta band. The increase in basal gamma was not 
      blocked by treatment with a conventional antipsychotic. No other treatment group 
      was able to fully reproduce this pattern in the mice. CONCLUSIONS: 
      Ketamine-induced alterations in EEG power spectra are consistent with 
      abnormalities in the theta and gamma frequency ranges reported in patients with 
      schizophrenia. Our findings support the hypothesis that NMDAR hypofunction 
      contributes to the deficits in schizophrenia and that the dopaminergic pathways 
      alone may not account for these changes.
FAU - Ehrlichman, R S
AU  - Ehrlichman RS
AD  - Stanley Center for Experimental Therapeutics in Psychiatry, Department of 
      Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Gandal, M J
AU  - Gandal MJ
FAU - Maxwell, C R
AU  - Maxwell CR
FAU - Lazarewicz, M T
AU  - Lazarewicz MT
FAU - Finkel, L H
AU  - Finkel LH
FAU - Contreras, D
AU  - Contreras D
FAU - Turetsky, B I
AU  - Turetsky BI
FAU - Siegel, S J
AU  - Siegel SJ
LA  - eng
GR  - P50 MH064045/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081028
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 690G0D6V8H (Ketamine)
RN  - CK833KGX7E (Amphetamine)
RN  - J6292F8L3D (Haloperidol)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Acoustic Stimulation/methods
MH  - Amphetamine/administration & dosage
MH  - Animals
MH  - Antipsychotic Agents/pharmacology
MH  - Biological Clocks/*drug effects
MH  - Central Nervous System Stimulants/administration & dosage
MH  - Disease Models, Animal
MH  - Drug Interactions
MH  - *Electroencephalography
MH  - Evoked Potentials, Auditory/*drug effects
MH  - Excitatory Amino Acid Antagonists/*adverse effects
MH  - Haloperidol/pharmacology
MH  - Ketamine/*adverse effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Reaction Time/drug effects
MH  - Risperidone/pharmacology
MH  - Schizophrenia/*chemically induced/drug therapy/physiopathology
EDAT- 2008/11/19 09:00
MHDA- 2009/04/16 09:00
CRDT- 2008/11/19 09:00
PHST- 2008/05/13 00:00 [received]
PHST- 2008/10/16 00:00 [revised]
PHST- 2008/11/14 00:00 [accepted]
PHST- 2008/11/19 09:00 [pubmed]
PHST- 2009/04/16 09:00 [medline]
PHST- 2008/11/19 09:00 [entrez]
AID - S0306-4522(08)01553-4 [pii]
AID - 10.1016/j.neuroscience.2008.10.031 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Jan 23;158(2):705-12. doi: 10.1016/j.neuroscience.2008.10.031. 
      Epub 2008 Oct 28.