The phencyclidine-glutamate model of schizophrenia.
Clinical neuropharmacology June 1, 1995 A L Halberstadt
The long-standing assumption that schizophrenia stems from chronic dopamine hyperactivity is questioned by a review of evidence. Direct examinations of schizophrenic brains have not found elevated dopamine levels, altered dopamine-related enzymes, or increased dopamine receptor concentrations or affinity, meaning no direct observations link psychosis to increased dopamine activity. The anesthetic drug phencyclidine (PCP), which induces psychosis-like states, acts as a glutamate antagonist, and glutamatergic abnormalities have been detected in schizophrenic brains. This evidence suggests that glutamate hypofunction may be involved in psychotic pathology, and a functional link exists between glutamate and dopamine systems. The review concludes that dysfunctional glutamatergic pathways are involved in psychotic pathology.