Neurophysiological and neurochemical animal models of schizophrenia: focus on glutamate.
Deficits in N-methyl-d-aspartate receptor (NMDAR) function play a critical role in the pathophysiology of schizophrenia. Animal models are needed to investigate possible mechanisms underlying NMDA dysfunction in schizophrenia as well as development of new therapeutic approaches. A major difficulty in developing animal models for schizophrenia is the identification of quantifiable measures that can be tested in a similar fashion in both humans and animals. The majority of animal models utilize analogous measures, wherein species-specific behaviors are used as presumed parallel manifestations of a common underlying construct. In vivo microdialysis and electrophysiology represent two methodologies in which homologous measures can instead be obtained in both animals and humans. In both techniques, well-validated, NMDA-sensitive measures are analyzed in rodents using probes implanted directly into cortex or subcortical structures. We discuss the currently available data from studies that used these methods in non-human primate and rodent glutamate models. In addition, we emphasize the possible relevance of the amphetamine-challenge studies to positive symptoms and of EEG measures to cognitive deficits in schizophrenia.
Schizophrenia Research Center, Nathan Kline Institute for Psychiatric Research/New York University School of Medicine, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA.
Stephan
S
Bickel
Daniel C
DC
Javitt
D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory; D018698:Glutamic Acid / Q000502:physiology*; D000882:Haplorhini; D006801:Humans; D017551:Microdialysis; D016202:N-Methylaspartate / Q000502:physiology*; D051381:Rats; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D009435:Synaptic Transmission
D018698:Glutamic Acid; D016202:N-Methylaspartate; D000661:Amphetamine; D004298:Dopamine