Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine.
[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd = 0.50 +/- 0.04 vs. 0.24 +/- 0.02nM; mean +/- S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd = 0.50 +/- 0.07 vs. 0.50 +/- 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.
Naylor
L
L
Rebecca L. Cooper Laboratories, Mental Health Research Institute of Victoria, Parkville, Australia.
Dean
B
B
Opeskin
K
K
Pavey
G
G
Hill
C
C
Keks
N
N
Copolov
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001667:Binding, Competitive / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017374:Paroxetine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism* / Q000401:mortality; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D013405:Suicide; D014316:Tritium
D014150:Antipsychotic Agents; D002352:Carrier Proteins; D006220:Haloperidol; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; C493230:SLC6A4 protein, human; C493232:Slc6a4 protein, rat