Hippocampal 5-hydroxytryptamine receptors: abnormalities in postmortem brain from schizophrenic subjects

There is strong evidence that hippocampal 5-hydroxytryptamine (5-HT) systems are affected in schizophrenia and hence we have studied a number of markers of the 5-HT system in hippocampi from subjects with schizophrenia. Using in situ radioligand binding with autoradiography we measured [H-3]proplyamino-8-hydroxy- 1,2,3,4-tetrahydronapthalene, [H-3]ketanserin and [H-3]sumatriptan binding in hippocampi from 20 schizophrenic and 20 control subjects. There were significant decreases in the density of [H-3]ketanserin binding to the 5-HT2A receptor (5-HT2AR) in the Cornu Ammonis (CA) 3 (p = 0.006), CA 1 (stratum radiatum p = 0.02; pyramidal layer p = 0.0008) and subiculum (pyramidal layer p = 0.0004), as well as methiothepin-insensitive [H-3]sumatriptan binding to the 5-HTIFR in the CA 1 (p = 0.016), stratum radiatum/lacunosum moleculare (p = 0.04) and subiculum (p = 0.015) from subjects with schizophrenia. Therewereno differences in the densities of 5-HT1AR, 5-HT(1D)Ror 5-HT4R in hippocampi from subjects with schizophrenia. These data support the hypothesis that regionally specific reductions in the density of the 5-HT2AR and 5-HTIFR are a component of the pathological processes underlying schizophrenia. (C) 2004 Elsevier B.V. All rights reserved.