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

• Published in: Bipolar disorders Vol. 5; no. 4; pp. 257 - 264
• Main Authors: Scarr, E, Pavey, G, Sundram, S, MacKinnon, A, Dean, B
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.08.2003
• Subjects: Adult; Aged; Analysis of Variance; Binding Sites; Binding, Competitive - physiology; bipolar disorder; Bipolar Disorder - metabolism; Cohort Studies; Female; glutamate; glutamic acid; hippocampus; Hippocampus - metabolism; Humans; Male; Middle Aged; psychiatric disorders; Radioligand Assay - instrumentation; receptors; Receptors, AMPA - metabolism; Receptors, Kainic Acid - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism
• ISSN: 1398-5647; 1399-5618
• DOI: 10.1034/j.1399-5618.2003.00024.x

Objectives:  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.