A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder

Brian Dean, Geoffrey Pavey, Mark McLeod, Kenneth Opeskin, Nicholas Keks, David Copolov

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Abstract

Background: This study examines the hypothesis that there are changes in cortical serotonergic, GABAergic and glutamatergic systems in bipolar disorder and schizophrenia. Methods: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n=8 per group). Results: Compared to tissue from schizophrenic (mean±S.E.M, 385±44 fmol/mg ETE) and control (383±44 fmol/mg ETE) subjects, there was an increase in the density of [3H]flumazenil binding to the benzodiazepine binding site on the GABAA receptor in subjects with bipolar disorder (451±17 fmol/mg ETE; P<0.05). There was no difference in the density of [3H]muscimol binding to the GABAA receptor or in the density of the serotonin1A receptor, serotonin2A receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [3H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. Limitations: This study involved a relatively small number of individuals. Conclusions: An increase in the γ2-receptor sub-unit in the GABAA receptor has been shown to increase benzodiazepine but not [3H]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABAA receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia.

Original languageEnglish
Pages (from-to)147-158
Number of pages12
JournalJournal of Affective Disorders
Volume66
Issue number2-3
DOIs
Publication statusPublished - 9 Oct 2001

Keywords

  • Bipolar disorder
  • GABA
  • GABA receptor
  • Glutamate
  • Schizophrenia
  • Serotonin

Cite this

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title = "A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder",
abstract = "Background: This study examines the hypothesis that there are changes in cortical serotonergic, GABAergic and glutamatergic systems in bipolar disorder and schizophrenia. Methods: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n=8 per group). Results: Compared to tissue from schizophrenic (mean±S.E.M, 385±44 fmol/mg ETE) and control (383±44 fmol/mg ETE) subjects, there was an increase in the density of [3H]flumazenil binding to the benzodiazepine binding site on the GABAA receptor in subjects with bipolar disorder (451±17 fmol/mg ETE; P<0.05). There was no difference in the density of [3H]muscimol binding to the GABAA receptor or in the density of the serotonin1A receptor, serotonin2A receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [3H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. Limitations: This study involved a relatively small number of individuals. Conclusions: An increase in the γ2-receptor sub-unit in the GABAA receptor has been shown to increase benzodiazepine but not [3H]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABAA receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia.",
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A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder. / Dean, Brian; Pavey, Geoffrey; McLeod, Mark; Opeskin, Kenneth; Keks, Nicholas; Copolov, David.

In: Journal of Affective Disorders, Vol. 66, No. 2-3, 09.10.2001, p. 147-158.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder

AU - Dean, Brian

AU - Pavey, Geoffrey

AU - McLeod, Mark

AU - Opeskin, Kenneth

AU - Keks, Nicholas

AU - Copolov, David

PY - 2001/10/9

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N2 - Background: This study examines the hypothesis that there are changes in cortical serotonergic, GABAergic and glutamatergic systems in bipolar disorder and schizophrenia. Methods: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n=8 per group). Results: Compared to tissue from schizophrenic (mean±S.E.M, 385±44 fmol/mg ETE) and control (383±44 fmol/mg ETE) subjects, there was an increase in the density of [3H]flumazenil binding to the benzodiazepine binding site on the GABAA receptor in subjects with bipolar disorder (451±17 fmol/mg ETE; P<0.05). There was no difference in the density of [3H]muscimol binding to the GABAA receptor or in the density of the serotonin1A receptor, serotonin2A receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [3H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. Limitations: This study involved a relatively small number of individuals. Conclusions: An increase in the γ2-receptor sub-unit in the GABAA receptor has been shown to increase benzodiazepine but not [3H]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABAA receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia.

AB - Background: This study examines the hypothesis that there are changes in cortical serotonergic, GABAergic and glutamatergic systems in bipolar disorder and schizophrenia. Methods: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n=8 per group). Results: Compared to tissue from schizophrenic (mean±S.E.M, 385±44 fmol/mg ETE) and control (383±44 fmol/mg ETE) subjects, there was an increase in the density of [3H]flumazenil binding to the benzodiazepine binding site on the GABAA receptor in subjects with bipolar disorder (451±17 fmol/mg ETE; P<0.05). There was no difference in the density of [3H]muscimol binding to the GABAA receptor or in the density of the serotonin1A receptor, serotonin2A receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [3H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. Limitations: This study involved a relatively small number of individuals. Conclusions: An increase in the γ2-receptor sub-unit in the GABAA receptor has been shown to increase benzodiazepine but not [3H]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABAA receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia.

KW - Bipolar disorder

KW - GABA

KW - GABA receptor

KW - Glutamate

KW - Schizophrenia

KW - Serotonin

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