Trafficking of neurokinin-1 receptors in serotonin neurons is controlled by substance P within the rat dorsal raphe nucleus
- 1 June 2009
- journal article
- research article
- Published by Wiley in European Journal of Neuroscience
- Vol. 29 (12), 2303-2314
- https://doi.org/10.1111/j.1460-9568.2009.06775.x
Abstract
Substance P (SP) modulates serotonin neurotransmission via neurokinin-1 receptors (NK1rs), and exerts regulatory effects on mood through habenular afferents to the dorsal raphe nucleus (DRN). We have previously demonstrated that, in the caudal DRN of rat, some serotonin neurons are endowed with NK1rs that are mostly cytoplasmic, whereas these receptors are mostly membrane bound in non-serotonin neurons. Here, we first examined by double-labeling immunocytochemistry the relationships between SP axon terminals and these two categories of DRN neurons. Almost half of the SP terminals were synaptic and many were in close contact with serotonin dendrites, but never with non-serotonin dendrites. In additional double-immunolabeling experiments, most if not all dendrites bearing membranous NK1rs appeared to be GABAergic. Treatment with the selective neurokinin-1 antagonist RP67580 modified the subcellular distribution of NK1rs in serotonin neurons. At 1 h after administration of a single dose, the receptor distribution was unchanged in both dendritic types but, after daily administration for 7 or 21 days, the plasma membrane and cytoplasmic density of NK1rs were increased in serotonin dendrites, without any change in non-serotonin dendrites. These treatments also increased NK1r gene expression in the caudal DRN. Lastly, a marked increase in the membrane (but not cytoplasmic) density of NK1rs was measured in serotonin dendrites after bilateral habenular lesion. These results suggest that the trafficking of NK1rs represents a cellular mechanism in control of the modulation of serotonin neuron activity by SP in DRN.Keywords
This publication has 80 references indexed in Scilit:
- Ubiquitin-dependent Down-regulation of the Neurokinin-1 ReceptorJournal of Biological Chemistry, 2006
- Substance P (Neurokinin 1) Receptor Antagonists Enhance Dorsal Raphe Neuronal ActivityJournal of Neuroscience, 2002
- Cellular basis for the effects of substance P in the periaqueductal gray and dorsal raphe nucleusJournal of Comparative Neurology, 2002
- Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and ß-arrestin proteinsProgress in Neurobiology, 2001
- The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stressBrain Research, 2001
- Contrasting Patterns and Cellular Specificity of Transcriptional Regulation of the Nuclear Receptor Nerve Growth Factor‐Inducible B by Haloperidol and Clozapine in the Rat ForebrainJournal of Neurochemistry, 2000
- Primary Afferent Fibers That Contribute to Increased Substance P Receptor Internalization in the Spinal Cord After InjuryJournal of Neurophysiology, 1999
- The neostriatal mosaic: Basis for the changing distribution of neurokinin-1 receptor immunoreactivity during developmentJournal of Comparative Neurology, 1996
- Higher potency of RP 67580, in the mouse and the rat compared with other nonpeptide and peptide tachykinin NK1 antagonistsBritish Journal of Pharmacology, 1993
- Synaptic remodeling of serotonin axon terminals in rat agranular cerebellumBrain Research, 1981