Serotonin(2A) receptors are reduced in the planum temporale from subjects with schizophrenia.
[(3)H]ketanserin binding to 5HT(2A) receptors was measured in the left planum temporale (sensory speech cortex) from schizophrenic and non-schizophrenic (control) subjects using both particulate membranes and tissue sections. There was a significant decrease in the affinity of [(3)H]ketanserin binding to particulate membranes from schizophrenic subjects who were treated with phenothiazines up to death. Adding 2nM chlorpromazine to brain tissue from control subjects caused a similar decrease in the affinity of [(3)H]ketanserin binding to particulate membranes. This suggests that the decrease in affinity observed in the phenothiazine-treated subjects was due to residual drugs. In addition, there was a significant decrease in the density of [(3)H]ketanserin binding in both particulate membranes and tissue sections from schizophrenic subjects which did not appear to be due to residual antipsychotic drugs. Analysis of the laminar distribution of 5HT(2A) receptors showed that this decrease was greatest in cortical layer III. The decrease in the density of 5HT(2A) receptors was significant whether schizophrenic subjects were receiving phenothiazines or haloperidol at the time of death, and there was no correlation between the last recorded dose of antipsychotic drug and 5HT(2A) receptor density. These data suggest that a decrease in the density of 5HT(2A) receptors in the planum temporale may be associated with the pathology of schizophrenia.
Pralong
D
D
The Rebecca L. Cooper Research Laboratories, The Division of Molecular Schizophrenia, The Mental Health Research Institute, Victoria 3052, Parkville, Australia. dfp@mhri.edu.au
Tomaskovic-Crook
E
E
Opeskin
K
K
Copolov
D
D
Dean
B
B
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001345:Autoradiography; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010640:Phenothiazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000032:analysis* / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000473:pathology; D013702:Temporal Lobe / Q000187:drug effects / Q000473:pathology*
D014150:Antipsychotic Agents; D010640:Phenothiazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D006220:Haloperidol