Serotonin2 receptors and the serotonin transporter in the schizophrenic brain.
The binding of [3H]paroxetine and [3H]ketanserin to particulate membranes from frontal cortex of subjects who had or did not have schizophrenia was measured as was [3H]paroxetine binding to particulate membranes from the hippocampus and caudate nucleus. There was no change in either the affinity or density of [3H]ketanserin binding to membranes from the frontal cortex of subjects who had schizophrenia. Similarly, there was no difference in the density of [3H]paroxetine binding to membranes from subjects who had or did not have schizophrenia. The affinity of [3H]paroxetine binding in the frontal cortex and putamen did not differ in subjects who had schizophrenia. By contrast, there was a significant decrease in the affinity of [3H]paroxetine binding to the hippocampal membrane from subjects who had schizophrenia (0.40 +/- 0.06 nM vs 0.26 +/- 0.02 nM; p < 0.05). Furthermore, this difference was more apparent in the subjects who had schizophrenia and committed suicide (0.49 +/- 0.09 nM) than it was in those who had schizophrenia but did not commit suicide (0.32 +/- 0.09 nM). As [3H]ketanserin binds to the serotonin2 receptor our data suggest that this receptor is not changed in the Brodmann's area 9 of the frontal cortex. By contrast, [3H]paroxetine binds to the serotonin transporter and therefore our data suggest that the serotonin transporter is altered in the hippocampus of subjects with schizophrenia.
Dean
B
B
Rebecca L. Cooper Laboratories, Mental Health Research Institute of Victoria, Parkville, Australia.
Hayes
W
W
Opeskin
K
K
Naylor
L
L
Pavey
G
G
Hill
C
C
Keks
N
N
Copolov
D L
DL
D000293:Adolescent; D000328:Adult; D000368:Aged; D001923:Brain Chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism
D002352:Carrier Proteins; D007650:Ketanserin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human