The thrust of this neuroscience research center proposal will be to elucidate neurobiological components of schizophrenia. The research center involves both clinical and preclinical investigations delineating neurobiological brain abnormalities in schizophrenia and the actions of psychotic drugs. Through the use of this center research scientists will collaborate to study these problems at the anatomical, immunocytochemical molecular neurobiological, biochemical, neurophysiological, clinical and behavior levels. Two general themes will be investigated: 1) brain abnormalities in adult schizophrenic patients and fetuses at high risk for schizophrenia and 2) phencyclidine (PCP) as a model for schizophrenia and the design of investigations around this model. The first line of research involves an anatomical survey of potential forebrain pathology comparing anatomical and immunocytochemical features of targeted areas of the brain. The second PCP research area involves the study of the PCP NMDA receptor complex in high risk fetal and adult schizophrenic brains as compared to controls, PET studies of patients abusing PCP, development of a ligand for the PCP and NMDA site in man, the study of alpha endopsychosin in high risk fetal and adult schizophrenic brains and the investigation of CSF in schizophrenic patients. Alterations in dopamine is a current theory of neurotransmitter pathology in schizophrenia. D1 and D2 receptors will be studied in animals and high risk fetal and adult schizophrenic brains along with their interaction with excitatory amino acids. Novel treatment strategies for PCP psychosis are suggested.