STRESS-INDUCED CHANGES IN MESSENGER-RNA LEVELS OF N-METHYL-D-ASPARTATE AND AMPA RECEPTOR SUBUNITS IN SELECTED REGIONS OF THE RAT HIPPOCAMPUS AND HYPOTHALAMUS

The postsynaptic AMPA/kainate and N-methyl-D-aspartate-selective gluta mate receptors are formed by several different subunits and the overal l subunit composition of the receptor appears to determine its physiol ogical and pharmacological properties. Although glutamatergic mechanis ms have been implicated in various forms of hippocampal stress respons es, the impact of stress on glutamate receptor subunit composition has not yet been elucidated, We have used cell-by-cell quantitative ill s itu hybridization to assess stress-induced changes in transcript level s of N-methyl-D-aspartate and AMPA receptor subunit genes in subdivisi ons of the rat hippocampus and hypothalamus that are implicated in the stress response, We found that 24 h after a single immobilization str ess there was a significant increase in the cellular level of NR1 subu nit messenger RNA (about 35-45% above control values) in hippocampal C A3 and CA1 pyramidal cells as well as in neurons of the hypothalamic s upraoptic and paraventricular nuclei, Moreover, in the CA3 area we hav e detected a concomitant increase (50% above controls) in the level of NR2B subunit messenger RNA, while the expression of NR2A subunit gene did not change after stress. Stress induced a selective decrease in t he level of AMPA receptor subunit glutamate receptorA messenger RNA in neurons of both the CA3 and CA1 areas (18 and 24%, respectively, belo w control values). These results suggest that the regulation of specif ic subunit messenger RNAs of the N-methyl-D-aspartate and AMPA recepto rs may be involved in altered hippocampal and hypothalamic responsiven ess to glutamate and thus could play a critical role in stress-induced changes in their function.