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

« Previous Next »Journal of Affective Disorders
Volume 66, Issue 2 , Pages 147-158, October 2001

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
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia
- Department of Pathology, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
- Department of Psychiatry, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
- Monash Department of Psychological Medicine, The Alfred, Prahran, Victoria, Australia
- Corresponding author. Tel.: +61-3-9388-1633; fax: +61-3-9387-5061
Geoffrey Pavey
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia
Mark McLeod
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia
- Department of Pathology, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
Kenneth Opeskin
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia
Nicholas Keks
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia
- Monash Department of Psychological Medicine, The Alfred, Prahran, Victoria, Australia
David Copolov
- The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia
- Department of Psychiatry, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
- Monash Department of Psychological Medicine, The Alfred, Prahran, Victoria, Australia

Received 1 April 2000; received in revised form 24 July 2000; accepted 4 August 2000.

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 GABA_A 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 GABA_A receptor or in the density of the serotonin_1A receptor, serotonin_2A 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 GABA_A 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 GABA_A 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.