A change in the density of [(3)H]flumazenil, but not [(3)H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder.
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 [(3)H]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 [(3)H]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 [(3)H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects.


CONCLUSIONS
This study involved a relatively small number of individuals.


CONCLUSIONS
An increase in the gamma2-receptor sub-unit in the GABA(A) receptor has been shown to increase benzodiazepine but not [(3)H]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.
Dean
B
B
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, The University of Melbourne, Parkville, Victoria, Australia. B.Dean@papyrus.mhri.edu.au
Pavey
G
G
McLeod
M
M
Opeskin
K
K
Keks
N
N
Copolov
D
D
D000328:Adult; D000368:Aged; D001345:Autoradiography; D001714:Bipolar Disorder / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D005442:Flumazenil / Q000493:pharmacokinetics*; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009118:Muscimol / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000378:metabolism*; D012559:Schizophrenia / Q000473:pathology*
D011963:Receptors, GABA-A; D009118:Muscimol; D005442:Flumazenil