Elsevier

Schizophrenia Research

Volume 71, Issues 2–3, 1 December 2004, Pages 383-392
Schizophrenia Research

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

https://doi.org/10.1016/j.schres.2004.02.007Get rights and content

Abstract

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 [3H]proplyamino-8-hydroxy-1,2,3,4-tetrahydronapthalene, [3H]ketanserin and [3H]sumatriptan binding in hippocampi from 20 schizophrenic and 20 control subjects. There were significant decreases in the density of [3H]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 [3H]sumatriptan binding to the 5-HT1FR in the CA 1 (p=0.016), stratum radiatum/lacunosum moleculare (p=0.04) and subiculum (p=0.015) from subjects with schizophrenia. There were no differences in the densities of 5-HT1AR, 5-HT1DR or 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-HT1FR are a component of the pathological processes underlying schizophrenia.

Section snippets

Materials and methods

2-(N,N-Di[2,3(n)-3H]proplyamino-8-hydroxy-1,2,3,4-tetrahydronapthalene ([3H]8-OH-DPAT), [3H]sumatriptan, [3H]GR113808 and [3H]microscales™ were obtained from Amersham Biosciences whilst [3H]ketanserin hydrochloride was obtained from New England Nuclear. BAS-TR© plates came from Fuji Photo Film, Tokyo, Japan. Serotonin hydrochloride, methiothepin hemioxalate and spiperone hydrochloride were purchased from Sigma Aldrich, as were all other laboratory reagents.

Results

All data sets were shown not to differ from a Gaussian distribution.

Discussion

Under the conditions used in this study [3H]8-OH-DPAT would bind predominantly to the 5-HT1AR (Dean et al., 1999), [3H]ketanserin to the 5-HT2AR (Dean and Hayes, 1996), [3H]GR 11808 to the 5-HT4R (Dean et al., 1999) and [3H]sumatriptan to both the 5-HT1DR and 5-HT1FR (Pascual et al., 1996). Hence, as in two previous studies Burnet et al., 1996, Hashimoto et al., 1991, our data failed to show a change in the density of 5-HT1A R in the hippocampus from subjects with schizophrenia. These findings

Acknowledgements

This research was funded by NH&MRC Project Grant #114253, The Victorian State Government and The Rebecca L. Cooper Medical Research Foundation. The authors thank Jaclyn McKenzie and Robyn Bradbury for their technical assistance as well as Chris Hill, Nicholas Keks and Ken Opeskin for their contributions to tissue collection and postmortem diagnosis.

References (37)

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