Research article summary (published 24 May 2009):

Trafficking of neurokinin-1 receptors in serotonin neurons is controlled by substance P within the rat dorsal raphe nucleus.

Full 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.

Author information

Author/s: Lacoste, Baptiste (B); Riad, Mustapha (M); Ratté, Marc-Olivier (MO); Boye, Sandra M (SM); Lévesque, Daniel (D); Descarries, Laurent (L);

Affiliation: Department of Pathology and Cell Biology, Université de Montréal, 2900 Blvd Edouard-Montpetit, Montreal, Quebec, Canada.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2009-Jun; vol 29 (issue 12) : pp 2303-14

Dates: Created 2009/07/09; Completed 2009/09/28;

PMID: 19490080, status: MEDLINE (last retrieval date: 9/28/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Analgesics - pharmacology Animals Cell Membrane - drug effects; metabolism; ultrastructure Dendrites - drug effects; metabolism; ultrastructure Drug Administration Schedule Habenula - physiology Immunohistochemistry Isoindoles - pharmacology Male Mesencephalon - cytology; metabolism Neural Pathways - cytology; metabolism

Neurons - cytology; drug effects; metabolism Protein Transport - drug effects; physiology Raphe Nuclei - cytology; metabolism Rats Rats, Sprague-Dawley Receptors, Neurokinin-1 - antagonists & inhibitors; metabolism Serotonin - metabolism Substance P - metabolism Synapses - drug effects; metabolism; ultrastructure Synaptic Transmission - drug effects; physiology gamma-Aminobutyric Acid - metabolism

Associated Chemicals: Analgesics (0) ; Isoindoles (0) ; Receptors, Neurokinin-1 (0) ; RP 67580 (135911-02-3) ; Substance P (33507-63-0) ; Serotonin (50-67-9) ; gamma-Aminobutyric Acid (56-12-2)

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