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 ± 0.02 nM; 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 ± 0.04 nM). 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 [³Hlparoxetine 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.