title: Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: a [3H]NGD-94-1 study.
abstract: Using an indirect subtraction binding technique and human postmortem tissue, several laboratories reported finding increases in dopamine D4 receptors in caudate nuclei of schizophrenic patients, although others have not replicated these findings. NGD-94-1 is a selective D4 antagonist with low affinity for the D2 and D3 receptors. [3H]NGD-94-1 has been used in this study to directly determine the density of D4 receptors in normals (n = 13) and schizophrenic subjects (n = 7) off antipsychotic drugs for at least 3 months prior to death, or on antipsychotic (n = 7) drugs at the time of death. Human postmortem coronal brain sections were incubated with [3H]NGD-94-1 and autoradiograms developed; and binding in pertinent regions was quantified. In normals, the highest density of [3H]NGD-94-1 binding was in the hippocampus (68 fmol mg(-1), temporal (33), insular (30), and entorhinal cortices (24.9). Significant increases in [3H]NGD-94-1 density in schizophrenics (n = 14) vs normals (n = 13) were observed in the entorhinal cortex (46%) at both low and high magnifications. The increases observed in the schizophrenics were found in both schizophrenics off antipsychotic drugs for at least 3 months prior to death and those on antipsychotic drugs at the time of death. Thus, the changes may be disease-related and not a consequence of pharmacological treatment. No significant differences were found between the two schizophrenic groups in any brain area studied.
authors.affiliation: Maryland Psychiatric Research Center, Baltimore, MD 21228, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Lahti
authors.forename: R C
authors.initials: RC
authors.lastname: Roberts
authors.forename: E V
authors.initials: EV
authors.lastname: Cochrane
authors.forename: R J
authors.initials: RJ
authors.lastname: Primus
authors.forename: D W
authors.initials: DW
authors.lastname: Gallager
authors.forename: R R
authors.initials: RR
authors.lastname: Conley
authors.forename: C A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001344:Autopsy; D001345:Autoradiography / Q000379:methods; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D018728:Entorhinal Cortex / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D009928:Organ Specificity; D011743:Pyrimidines / Q000493:pharmacokinetics*; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D050638:Receptors, Dopamine D4; D012016:Reference Values; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014316:Tritium
chemical_list: D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D007093:Imidazoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D014316:Tritium; D050638:Receptors, Dopamine D4; C107692:NGD 94-1