Stress-induced dendritic internalization and nuclear translocation of the neurokinin-3 (NK3) receptor in vasopressinergic profiles of the rat paraventricular nucleus of the hypothalamus

Abstract

Central neuronal circuits that relay stress information include vasopressin- (AVP) and oxytocin- (OC) containing neurons of the paraventricular nucleus of the hypothalamus (PVN). These neurons are potentially modulated by neurokinin-3 receptors (NK3Rs) of the tachykinin family of neuropeptides. NK3Rs have been localized in PVN neurons and have showed nuclear translocation following an osmotic challenge in rodents. However, their subcellular distribution in AVP or OC neurons of the PVN and plasticity following restraint stress in rats are unknown. In the present study, densities of NK3Rs in PVN AVP- or OC-labeled somatodendritic profiles were measured by quantitative immunoelectron microscopy in control or stressed rats. In resting conditions, NK3Rs were predominantly located in AVP neurons, however sparsely distributed in OC neurons of the PVN. All NK3-labeled somata of the PVN in control rats showed cytoplasmic but no nuclear immunolabeling. An acute restraint stress session of 30min significantly increased nuclear NK3R density in AVP-labeled somata but not in OC-labeled somata. These changes were accompanied by a respective decrease and increase in plasmalemmal and cytoplamic NK3R densities in AVP-labeled but not in OC-labeled dendrites. The results of this study suggest that in the rat PVN 1) NK3R distribution is conducive to modulation of systemic and/or central AVP release through PVN inputs to the posterior pituitary and/or the amygdala and 2) acute restraint stress activates (internalizes) NK3Rs on surface and evokes nuclear NK3R translocation exclusively in AVP neurons. This trafficking might contribute to neurochemical imbalances observed in neuronal circuits involved in stress-related disorders such as anxiety.