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 Citations (Scopus)

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.

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

Fingerprint

Dopamine D4 Receptors
Antipsychotic Agents
Brain
Entorhinal Cortex
Subtraction Technique
Caudate Nucleus
Cerebral Cortex
Hippocampus
NGD 94-1
Pharmacology
Pharmaceutical Preparations

Keywords

  • D receptor
  • Dopamine
  • Human
  • Postmortem
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Lahti, R. A., Roberts, R. C., Cochrane, E. V., Primus, R. J., Gallager, D. W., Conley, R. R., & Tamminga, C. A. (1998). Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: A [3H]NGD-94-1 study. Molecular Psychiatry, 3(6), 528-533.

Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue : A [3H]NGD-94-1 study. / Lahti, R. A.; Roberts, R. C.; Cochrane, E. V.; Primus, R. J.; Gallager, D. W.; Conley, R. R.; Tamminga, C. A.

In: Molecular Psychiatry, Vol. 3, No. 6, 1998, p. 528-533.

Research output: Contribution to journalArticle

Lahti, RA, Roberts, RC, Cochrane, EV, Primus, RJ, Gallager, DW, Conley, RR & Tamminga, CA 1998, 'Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: A [3H]NGD-94-1 study', Molecular Psychiatry, vol. 3, no. 6, pp. 528-533.
Lahti RA, Roberts RC, Cochrane EV, Primus RJ, Gallager DW, Conley RR et al. Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: A [3H]NGD-94-1 study. Molecular Psychiatry. 1998;3(6):528-533.
Lahti, R. A. ; Roberts, R. C. ; Cochrane, E. V. ; Primus, R. J. ; Gallager, D. W. ; Conley, R. R. ; Tamminga, C. A. / Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue : A [3H]NGD-94-1 study. In: Molecular Psychiatry. 1998 ; Vol. 3, No. 6. pp. 528-533.
@article{8cba30c9b8af417c87a221e1a3ff0782,
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.",
keywords = "D receptor, Dopamine, Human, Postmortem, Schizophrenia",
author = "Lahti, {R. A.} and Roberts, {R. C.} and Cochrane, {E. V.} and Primus, {R. J.} and Gallager, {D. W.} and Conley, {R. R.} and Tamminga, {C. A.}",
year = "1998",
language = "English (US)",
volume = "3",
pages = "528--533",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue

T2 - A [3H]NGD-94-1 study

AU - Lahti, R. A.

AU - Roberts, R. C.

AU - Cochrane, E. V.

AU - Primus, R. J.

AU - Gallager, D. W.

AU - Conley, R. R.

AU - Tamminga, C. A.

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - D receptor

KW - Dopamine

KW - Human

KW - Postmortem

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0031789963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031789963&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 528

EP - 533

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 6

ER -