Phencyclidine Model of Frontal Cortical Dysfunction in Nonhuman Primates

Long-term use of drugs like phencyclidine (PCP), which block NMDA glutamate receptors, can produce schizophrenia-like symptoms in people and abnormal behavior in animals. This review evaluates how well PCP-induced animal behaviors model human psychotic disorders and presents a hypothesis about PCP's effects on the prefrontal cortex. The behavioral and neurochemical changes caused by PCP suggest that altered interactions between glutamate and dopamine systems in the prefrontal cortex may contribute to the cognitive problems seen in schizophrenia.

Study at a glance

Abstract

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.