Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: A [3H]NGD-94-1 study

R. A. Lahti, R. C. Roberts, E. V. Cochrane, R. J. Primus, D. W. Gallager, R. R. Conley, C. A. Tamminga

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Using an indirect subtraction binding technique and human postmortem tissue, several laboratories1-3 reported finding increases in dopamine D4 receptors in caudate nuclei of schizophrenic patients, although others4-6 have not replicated these findings. NGD-94-1 is a selective D4 antagonist with low affinity for the D2 and D3 receptors.7,8 [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.

Original languageEnglish (US)
Pages (from-to)528-533
Number of pages6
JournalMolecular psychiatry
Volume3
Issue number6
DOIs
StatePublished - Jan 1 1998

Keywords

  • D receptor
  • Dopamine
  • Human
  • Postmortem
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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