Trafficking of neurokinin-1 receptors in serotonin neurons is controlled by substance P within the rat dorsal raphe nucleus.
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.
Lacoste
Baptiste
B
Department of Pathology and Cell Biology, Université de Montréal, 2900 Blvd Edouard-Montpetit, Montreal, Quebec, Canada.
Riad
Mustapha
M
Ratté
Marc-Olivier
MO
Boye
Sandra M
SM
Lévesque
Daniel
D
Descarries
Laurent
L
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004334:Drug Administration Schedule; D019262:Habenula / Q000502:physiology; D007150:Immunohistochemistry; D054833:Isoindoles / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000700:Analgesics; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D012701:Serotonin; D013373:Substance P; D005680:gamma-Aminobutyric Acid