Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder.
OBJECTIVE
The purpose of this study was to determine whether there are changes in the density of ionotropic glutamate receptors in the hippocampus of subjects with bipolar disorder.


METHODS
Using in situ radioligand binding with semiquantitative autoradiography, we measured the density of [3H]MK-801, [3H]CGP39653, [3H]AMPA and [3H]kainate binding in hippocampi, obtained postmortem, from eight subjects with type 1 bipolar disorder and 8 age- and sex-matched controls.


RESULTS
In subjects with bipolar disorder there were significant decreases in the density of [3H]MK-801 binding in the Cornu Ammonis (CA) 3 (mean +/- SEM; 108.8 +/- 12.2 versus 166.2 +/- 18.0 fmol/mg ETE, p < 0.005) as well as the pyramidal (102.8 +/- 9.2 versus 136.6 +/- 11.2 fmol/mg ETE, p < 0.05) and polymorphic (21.73 +/- 6.5 versus 53.26 +/- 11.6 fmol/mg ETE, p < 0.05) layers of the subiculum. In addition, two-way analysis of variance (ANOVA) revealed a decrease in the density of [3H]CGP39653 binding across the hippocampal formation in bipolar subjects, which did not reach significance in any subregion. There were no changes in the densities of [3H]AMPA or [3H]kainate binding in these subjects.


CONCLUSIONS
[3H]CGP39653 and [3H]MK-801 bind to the glutamate binding site and open ion channel of the n-methyl-d-aspartate (NMDA) receptor, respectively. Therefore, these data suggest that there is a decrease in the number of open ion channels associated with no significant change in the apparent density of NMDA receptors in regions of the hippocampus from subjects with bipolar disorder.
Scarr
E
E
Rebecca L. Cooper Research Laboratories, Mental Health Research Institute, Parkville, Victoria, Australia. escarr@mhri.edu.au
Pavey
G
G
Sundram
S
S
MacKinnon
A
A
Dean
B
B
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001665:Binding Sites; D001667:Binding, Competitive / Q000502:physiology; D001714:Bipolar Disorder / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay / Q000295:instrumentation; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate