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 [(3)H]proplyamino-8-hydroxy-1,2,3,4-tetrahydronapthalene, [(3)H]ketanserin and [(3)H]sumatriptan binding in hippocampi from 20 schizophrenic and 20 control subjects. There were significant decreases in the density of [(3)H]ketanserin binding to the 5-HT(2A) receptor (5-HT(2A)R) 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 [(3)H]sumatriptan binding to the 5-HT(1F)R 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-HT(1A)R, 5-HT(1D)R or 5-HT(4)R in hippocampi from subjects with schizophrenia. These data support the hypothesis that regionally specific reductions in the density of the 5-HT(2A)R and 5-HT(1F)R are a component of the pathological processes underlying schizophrenia.
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Australia.
Elizabeth
E
Scarr
Geoffrey
G
Pavey
David
D
Copolov
Brian
B
Dean
D000328:Adult; D000368:Aged; D001345:Autoradiography; D001665:Binding Sites; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007650:Ketanserin / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics; D018170:Sumatriptan / Q000493:pharmacokinetics; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; D018170:Sumatriptan; D007650:Ketanserin