Long-term intake of noncompetitive N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine (PCP), can simulate schizophrenia-like symptomatology in human subjects and can produce aberrant behavior in animals. The behavioral changes produced by PCP in animals have been suggested to model certain primary symptoms of idiopathic psychotic disorders, and the neurobiological substrates affected by PCP have been implicated in the pathophysiology of schizophrenia. This review considers the validity of PCP-induced behaviors in animals as a model of the human disorder, and a developing hypothesis of PCP-induced neurochemical dysfunction within the prefrontal cortex is presented. The behavioral and neurochemical effects of PCP may support the notion that altered glutamatergic/dopaminergic interactions within prefrontal cortex contribute to the cognitive dysfunction of schizophrenia.
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