INCREASED EXPRESSION OF THE N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT, NR1, IN IMMUNOHISTOCHEMICALLY IDENTIFIED MAGNOCELLULAR HYPOTHALAMIC NEURONS DURING DEHYDRATION

N-Methyl-D-aspartate receptors are thought to be involved in synaptic signaling within the hypothalamo-neurohypophysial system, but the exte nt and nature of their involvement has not been determined. In this st udy, in the rat, we evaluated the effect of hyperosmotic stimulation o n the N-methyl-D-aspartate receptor subunit, NR1, which confers functi on to N-methyl-D-aspartate receptor heteromers. Co-localization of imm unoreactivity for NR1 and vasopressin- or oxytocin-associated neurophy sin in magnocellular neurons of the supraoptic and paraventricular hyp othalamic nuclei was accomplished using double-label immunohistochemis try. Our results show that vasopressin- and oxytocin-neurophysin-posit ive populations contained detectable levels of NR1 labeling. Using NR1 labeling as a measure of N-methyl-D-aspartate receptor density, we ex amined the effect of dehydration in these nuclei. Using computer-assis ted densitometry, we found significantly greater NR1 labeling densitie s in the magnocellular regions of both the supraoptic and paraventricu lar nuclei of saline-treated rats than of control rats. This increase was not due to methodological factors, since no changes in NR1 labelin g density were found in a nearby nucleus, the nucleus reuniens. Wester n blot analysis showed similar selective increases in NR1 labeling in homogenates from the supraoptic nucleus, paraventricular nucleus and i n some cases from the anterior hypothalamic area. In both immunohistoc hemical and western blotting experiments we did not observe a dehydrat ion-induced increase in NR1 in other brain areas examined. Our results showing an up-regulation of NR1-containing N-methyl-D-aspartate recep tors during dehydration suggest that these receptors are involved in t he regulation of body water and may represent an adaptive physiologica l response following activation of the hypothalamo-neurohypophysial ax is. In addition, these results suggest that the functional expression of N-methyl-D-aspartate receptors is dynamic and may be modified accor ding to the physiological slate of the animal. (C) 1997 IBRO.