Serotonin(2A) receptors are reduced in the planum temporale from subjects with schizophrenia

[H-3]ketanserin binding to 5HT(2A) receptors was measured in the left planu m temporale (sensory speech cortex) from schizophrenic and non-schizophreni c (control) subjects using both particulate membranes and tissue sections. There was a significant decrease in the affinity of [H-3]ketanserin binding to particulate membranes from schizophrenic subjects who were treated with phenothiazines up to death. Adding 2 nM chlorpromazine to brain tissue fro m control subjects caused a similar decrease in the affinity of [H-3]ketans erin binding to particulate membranes. This suggests that the decrease in a ffinity observed in the phenothiazine-treated subjects was due to residual drugs. In addition, there was a significant decrease in the density of [H-3 ]ketanserin binding in both particulate membranes and tissue sections from schizophrenic subjects which did not appear to be due to residual antipsych otic drugs. Analysis of the laminar distribution of 5HT(2A) receptors showe d that this decrease was greatest in cortical layer III. The decrease in th e density of 5HT(2A) receptors was significant whether schizophrenic subjec ts were receiving phenothiazines or haloperidol at the time of death, and t here was no correlation between the last recorded dose of antipsychotic dru g and 5HT(2A) receptor density. These data suggest that a decrease in the d ensity of 5HT(2A) receptors in the planum temporale may be associated with the pathology of schizophrenia. (C) 2000 Elsevier Science B.V. All rights r eserved.