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

Authors

  • Baptiste Lacoste,

    1. Department of Pathology and Cell Biology, Université de Montréal, 2900 Blvd Édouard-Montpetit, Montreal, Quebec, Canada H3T 1J4
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  • Mustapha Riad,

    1. Department of Pathology and Cell Biology, Université de Montréal, 2900 Blvd Édouard-Montpetit, Montreal, Quebec, Canada H3T 1J4
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  • Marc-Olivier Ratté,

    1. Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
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  • Sandra M. Boye,

    1. Department of Psychiatry, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
    2. Centre de Recherche Fernand-Seguin, Hôpital Louis-H. Lafontaine, Montreal, Quebec, Canada
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  • Daniel Lévesque,

    1. Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada
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  • Laurent Descarries

    1. Department of Pathology and Cell Biology, Université de Montréal, 2900 Blvd Édouard-Montpetit, Montreal, Quebec, Canada H3T 1J4
    2. Department of Physiology, Université de Montréal, Montreal, Quebec, Canada
    3. Groupe de recherche sur le système nerveux central, Université de Montréal, Montreal, Quebec, Canada
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Dr Laurent Descarries, 1Department of Pathology and Cell Biology, as above.
E-mail: laurent.descarries@umontreal.ca

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.

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