IONOTROPIC GLUTAMATE-RECEPTOR SUBTYPES IN THE AGED MEMORY-IMPAIRED AND UNIMPAIRED LONG-EVANS RAT

The comparative quantitative autoradiographic distribution of ionotrop ic glutamate receptor subtypes were investigated in young adults (six months), and aged (24-25 months) cognitively impaired and unimpaired m ale Long-Evans rats. Aged rats were behaviorally characterized as eith er cognitively impaired or unimpaired based upon their performances in the Morris water maze task compared to the young adult controls. The status of the N-methyl-D-aspartate, [I-125]dizocilpine maleate, [H-3]k ainate and amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA, [H-3] AMPA) receptor binding sites were then established in these three subg roups of animals as a function of their cognitive performance in the M orris water maze task. The apparent densities of both N-methyl-D-aspar tate/[I-125]dizocilpine maleate and kainate binding sites were signifi cantly decreased in various regions of the aged rat brain. Marked loss es in [I-125]dizocilpine maleate binding sites were observed in outer laminae of the frontal, parietal and temporal cortices, and the stratu m radiatum of the CA3 subfield of the hippocampus. Interestingly, loss es in [I-125]dizocilpine maleate binding sites were generally most evi dent in the cognitively unimpaired aged subgroup, suggesting a possibl e inverse relationship between losses of this receptor subtype and cog nitive performances in the Morris water maze task. The levels of [H-3] kainate binding were most significantly diminished in various cortical and hippocampal areas as well as the striatum and septal nuclei of bo th groups of aged rats. In contrast, the apparent density of [H-3]AMPA binding was increased in most hippocampal subfields and the superfici al laminae of the occipital cortex of the cognitively impaired vs youn g adult rats. Changes in [H-3]AMPA labeling failed to reach significan ce in the unimpaired cohort. Taken together, these results show that w hile losses in [H-3]kainate binding were similar in both subgroups of aged rats, differences were seen with respect to cognitive status for both [I-125]dizocilpine maleate/N-methyl-D-aspartate and [H-3]AMPA bin ding sites. Decreases in [I-125]dizocilpine maleate binding sites were mostly restricted to cortical areas of cognitively unimpaired rats, w hile increases in the AMPA binding subtype were seen in the memory-imp aired subgroup. It would thus appear that changes in N-methyl-D-aspart ate and AMPA receptor subtypes may be more critical than alterations i n kainate binding sites for the emergence of the functional deficits s een in the aged cognitively impaired rat. Copyright (C) 1996 IBRO. Pub lished by Elsevier Science Ltd.