Selective loss of cerebral cortical Sigma, but not PCP binding sites in schizophrenia

Abstract

Drugs such as phencyclidine (PCP) that interact with PCP and sigma binding sites can produce psychotomimetic effects that resemble some symptoms of schizophrenia. Therefore, it has been suggested that PCP and sigma receptors may be important in the clinical manifestations of schizophrenia. Assays of these two binding sites in human postmortem brains showed consistent significant reductions in the density of sigma, but not PCP sites, in schizophrenics as compared with age-matched and postmortem interval-matched normal and suicide controls. Reductions in the density of sigma binding sites in schizophrenia were most prominent in temporal cerebral cortex, and were accompanied by a small increase in affinity for the ligand [3H]haloperidol. These data provide the first evidence for alterations in sigma binding sites in schizophrenia, and suggest that selective sigma ligands may be useful in the treatment of the disorder.