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.