Cortical serotonin7, 1D and 1F receptors: effects of schizophrenia, suicide and antipsychotic drug treatment.
Abnormalities in serotonergic function are thought to be important in the pathology of schizophrenia. Postmortem CNS studies suggest that levels of serotonin receptors may be altered in the cortex of subjects with schizophrenia. Seeking to expand this hypothesis we have examined the effect of schizophrenia and antipsychotic drug treatments on the levels of cortical serotonin7, 1D and 1F receptors. There was a significant decrease in the binding of [3H]SB 269970 to the serotonin7 receptor in Brodmann's area 9 from subjects with schizophrenia compared to controls (Mean+/-S.E.M.: 8.3+/-0.76 vs. 11.0+/-0.64 fmol/mg ETE; p<0.05) and an increase in the binding of that radioligand in the cortex of rats treated with haloperidol (p=0.03). There were no significant differences in [3H]sumatriptan binding to the serotonin1D or serotonin1F receptor in Brodmann's area 9 from subjects with schizophrenia. There was a significant increase in [3H]sumatriptan binding to the serotonin1D in binding Layer 2 from subjects who had potentially died by suicide that was not present in other binding layers or for the serotonin1F or serotonin7 receptors. There was decrease in [3H]sumatriptan binding to the serotonin1D, but not serotonin1F, receptors across all cortical binding layers in rats treated with haloperidol. These data would be consistent with the hypothesis that decreased levels of serotonin7 receptors in Brodmann's area 9 may be involved in the pathological processes of schizophrenia and that levels of cortical serotonin7 and 1D receptors can be affected by antipsychotic drug treatment.
Dean
Brian
B
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, The University of Melbourne, Australia. bdean_mhri@iprimus.com.au
Pavey
Geoffrey
G
Thomas
David
D
Scarr
Elizabeth
E
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001665:Binding Sites; D016022:Case-Control Studies; D002746:Chlorpromazine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D044346:Receptor, Serotonin, 5-HT1D / Q000235:genetics* / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D013405:Suicide / Q000706:statistics & numerical data*; D018170:Sumatriptan / Q000378:metabolism; D000096642:Receptor, Serotonin, 5-HT1F
D014150:Antipsychotic Agents; D002746:Chlorpromazine; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D018170:Sumatriptan; D000096642:Receptor, Serotonin, 5-HT1F; C104425:serotonin 7 receptor