Schizophrenia is a chronic mental disorder in which delusions, hallucinations, loosening of thought, and cognitive dysfunctions may develop in early adulthood. Hypofunction of NMDA glutamate systems in the brain has been examined in the course of determining the pathophysiology of schizophrenia. Long-term administration of Psychostimulants such as cocaine, amphetamines and phencyclidine can induce behavioral sensitization, i.e., hyper-locomotion, stereotypy, and disturbances of social interaction, providing models relevant to the study of schizophrenia. We investigated the effects of both excitatory (glutamate) and inhibitory (GABA) amino acids on the development of behavioral sensitization induced by the psychostimulants. In addition, our recent post-mortem studies of schizophrenia suggested the neurobiological significance of glutamate and GABA receptors. Considering these findings in the animal models and schizophrenia, we discussed the dysfunctions of amino acid transmitter systems involved in the pathology of schizophrenia. Developing animal models that fully reproduce the expressed phenotype of schizophrenia is difficult, as schizophrenia is a complex mental disorder. While the challenge to define the mental and social components of a human disease is highly limited in animal models, significant information regarding the causes and mechanisms of schizophrenia can be based on findings obtained from animal models. Evaluation of model validity in addition to the precise mechanisms of biological interactions in neural networks will provide more valid suggestions regarding the underlying pathophysiology of schizophrenia and the strategies of treatment