Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder

Objectives: The purpose of this study was to determine whether 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 auto radiography I we measured the density of [H-3]MK-801, [H-3]CGP39653, [H-3]AMPA and [H-3]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 [H-3]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 [H-3]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 [H-3]AMPA or [H-3]kainate binding in these subjects. Conclusions: [H-3]CGP39653 and [H-3]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.