| Abstract No.: | A-B1041 |
| Country: | Canada |
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| Title: | EFFECT OF THE ANTAGONIST RP67580 ON THE SUBCELLULAR LOCALIZATION OF NK1 RECEPTORS IN THE DORSAL RAPHE NUCLEUS OF ADULT RAT. |
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| Authors/Affiliations: | 1 Baptiste Lacoste*; 1 Mustapha Riad; 1 Laurent Descarries;
1 Pathology & Cell Biology and Physiology, GRSNC, Faculty of Medicine, Université de Montréal, QC, Canada
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| Content: | Substance P (SP) axons originating from the lateral habenula innervate the dorsal raphe nucleus (DRN) of rat. In a recent, double immunolabeling study, we demonstrated the presence of SP NK1 receptors (NK1r) in a subpopulation of DRN serotonin (5-HT) neurons mostly located in the caudal half of the nucleus (Lacoste et al., 2006). In these neurons (cell bodies and dendrites), NK1r were mainly found in the cytoplasm, but they were mostly membrane-bound in intermingled non 5-HT dendrites (putative GABAergic). In rodents, treatment with NK1r antagonists increases the firing of DRN 5 HT neurons, presumably through a desensitization of 5-HT1A autoreceptors (Conley et al., 2002; Guiard et al., 2005). Here, we examined the effect of acute and subchronic treatment with the NK1r antagonist RP67580 on the subcellular localization of NK1r (gold-immunolabeled) in the caudal DRN. The tissue was processed 1 h after a single i.p. injection or after the last daily injection for 1 week of 5 mg/kg RP67580. The density of NK1r immunolabeling was measured by comparison with untreated controls, over the whole surface as well on the plasma membrane of both types of NK1r-labeled dendrites (5 HT and non 5-HT). After acute RP67580 treatment, there was a 40% increase in the overall density of NK1r labeling in 5-HT dendrites, without apparent effect on the density of their plasma membrane labeling or that of non 5-HT dendrites. After 1 week of treatment, the overall density of NK1r labeling was still increased at 140% of control, but there was also a significant increase (100%) in the density of the membrane labeling of 5-HT dendrites. Again, there were no changes in the labeling of non 5-HT dendrites. In doubly labeled material, we also noted that SP terminals were frequently located in the immediate vicinity of, or in synaptic contact with 5-HT (TpOH positive) dendrites or somata, which was never the case for non 5-HT dendrites. In addition to the close relationships between SP terminals and 5-HT soma-dendrites, the present demonstration of a trafficking of NK1r receptors to the plasma membrane of 5-HT neurons after subchronic treatment with the NK1r antagonist supports the hypothesis of a tonic activation and internalization of NK1r by nearby or synaptic release of SP onto DRN 5-HT neurons. The data also suggest that eventual GABA-mediated effects of habenular SP afferents on DRN 5-HT neurons might depend on a diffuse rather than synaptic transmission by SP. (Supported by CIHR grant NRF 3544). |
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