Quantitative autoradiography of dopamine-D1 receptors, D2 receptors, and dopamine uptake sites in postmortem striatal specimens from schizophrenic patients.
A number of previously published homogenate receptor binding studies have postulated that dopaminergic dysfunction in schizophrenia may be related to abnormalities in dopamine receptors. In this study, postmortem striatal specimens from patients with schizophrenia, normal controls, and psychiatric controls that had received neuroleptics were studied with quantitative autoradiography for dopamine receptors. Autoradiography with single concentrations of [3H]-SCH 23390 for D1 receptors, [3H]-raclopride for D2 receptors, and [3H]-CFT for dopamine uptake sites failed to define significant differences between the study groups. [3H]-CFT bound in a patchy distribution in the striatum that is believed to correspond to striosomal and matrix striatal compartments. There were no differences between groups when [3H]-CFT binding density was examined in the striosomal and matrix compartments. There were also no differences between groups in the percentage of striatal area occupied by striosomal or matrix compartments as defined by [3H]-CFT binding. We conclude that abnormalities of these dopamine receptor subtypes are probably not primary features of the schizophrenic syndrome in the brain collection examined. Previous reports of elevated D2 receptor binding in schizophrenia may have been related to drug treatment effects. Alternatively, the relatively high affinity of ligands used in previous studies for D4 receptors may explain the discrepancy in our findings. Unchanged [3H]-CFT binding in the schizophrenic group also suggests that the density of mesostriatal neuronal terminals is not altered in schizophrenia.
Knable
M B
MB
National Institute of Mental Health, Clinical Brain Disorders Branch, Washington, D.C. 20032.
Hyde
T M
TM
Herman
M M
MM
Carter
J M
JM
Bigelow
L
L
Kleinman
J E
JE
D001345:Autoradiography; D001552:Benzazepines / Q000627:therapeutic use; D001665:Binding Sites; D002452:Cell Count; D003342:Corpus Striatum / Q000737:chemistry* / Q000378:metabolism*; D046508:Culture Techniques; D006801:Humans; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000032:analysis* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism*; D012457:Salicylamides; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology*
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride