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Serotonin release from mesencephalic raphe neurons grafted to the 5,7-dihydroxytryptamine-lesioned rat hippocampus : Effects of behavioral activation and stress

Cenci, M. A. LU and Kalén, P. LU (2000) In Experimental Neurology 164(2). p.351-361
Abstract

Transplants of fetal midbrain raphe neurons into the adult brain have been shown to promote recovery of complex behavioral deficits in several experimental models, but the mechanisms underlying these effects are only partially understood. In the present study, we have used a well-characterized model system to ascertain whether midbrain raphe graft can display behaviorally relevant changes in transmitter release and/or metabolism. Fetal mesencephalic raphe neurons were grafted unilaterally into the hippocampus previously deprived of its innate serotonergic innervation by intraventricular injections of 5,7-dihydroxytryptamine. The contralateral hippocampus remained as a non-grafted, lesioned control. Microdialysis probes were implanted in... (More)

Transplants of fetal midbrain raphe neurons into the adult brain have been shown to promote recovery of complex behavioral deficits in several experimental models, but the mechanisms underlying these effects are only partially understood. In the present study, we have used a well-characterized model system to ascertain whether midbrain raphe graft can display behaviorally relevant changes in transmitter release and/or metabolism. Fetal mesencephalic raphe neurons were grafted unilaterally into the hippocampus previously deprived of its innate serotonergic innervation by intraventricular injections of 5,7-dihydroxytryptamine. The contralateral hippocampus remained as a non-grafted, lesioned control. Microdialysis probes were implanted in the hippocampus 5-7 months postgrafting. Under baseline conditions, extracellular levels of serotonin were similar to normal in the grafted hippocampi, but undetectable on the contralateral, non-grafted side. Levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were markedly higher than normal in the grafted hippocampi, but dramatically reduced on the contralateral nongrafted side. Handling stimulation (gentle stroking of a rat's fur and tail for 15 min) induced a 64% increase in serotonin output in the intact rats and a small but significant 12% increase in the grafted animals. Non-noxious tail-pinch (15 min) enhanced serotonin release by 86% in the intact rats and 28% in the grafted ones. Extracellular 5-HIAA levels remained unchanged during both handling and tail-pinch in both the intact and the grafted rats. Forced immobilization of the rats for 15 min induced a transient 124% increase in extracellular serotonin levels in the intact rats and a significant 19% increase in the grafted animals, whereas swimming in temperate water (25-30°C; 15 min) induced no detectable changes in serotonin output in any of the groups. 5-HIAA levels remained unchanged during forced immobilization, but were significantly reduced during the swimming session in both the intact (-38%) and grafted (-15%) animals. The present results indicate that median raphe grafts can become functionally integrated in the denervated host hippocampus and respond by altered indole output when the animal is exposed to different types of environmental challenges. © 2000 Academic Press.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
5-hydroxytryptamine, Functional integration, In vivo microdialysis, Intracerebral neural grafting, Transmitter release, Transplant
in
Experimental Neurology
volume
164
issue
2
pages
11 pages
publisher
Academic Press
external identifiers
  • scopus:0034535293
ISSN
0014-4886
DOI
10.1006/exnr.2000.7433
language
English
LU publication?
yes
id
12c1f6c0-327b-4b5d-8319-27d9660c0e34
date added to LUP
2017-04-24 13:11:11
date last changed
2017-04-24 13:11:11
@article{12c1f6c0-327b-4b5d-8319-27d9660c0e34,
  abstract     = {<p>Transplants of fetal midbrain raphe neurons into the adult brain have been shown to promote recovery of complex behavioral deficits in several experimental models, but the mechanisms underlying these effects are only partially understood. In the present study, we have used a well-characterized model system to ascertain whether midbrain raphe graft can display behaviorally relevant changes in transmitter release and/or metabolism. Fetal mesencephalic raphe neurons were grafted unilaterally into the hippocampus previously deprived of its innate serotonergic innervation by intraventricular injections of 5,7-dihydroxytryptamine. The contralateral hippocampus remained as a non-grafted, lesioned control. Microdialysis probes were implanted in the hippocampus 5-7 months postgrafting. Under baseline conditions, extracellular levels of serotonin were similar to normal in the grafted hippocampi, but undetectable on the contralateral, non-grafted side. Levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were markedly higher than normal in the grafted hippocampi, but dramatically reduced on the contralateral nongrafted side. Handling stimulation (gentle stroking of a rat's fur and tail for 15 min) induced a 64% increase in serotonin output in the intact rats and a small but significant 12% increase in the grafted animals. Non-noxious tail-pinch (15 min) enhanced serotonin release by 86% in the intact rats and 28% in the grafted ones. Extracellular 5-HIAA levels remained unchanged during both handling and tail-pinch in both the intact and the grafted rats. Forced immobilization of the rats for 15 min induced a transient 124% increase in extracellular serotonin levels in the intact rats and a significant 19% increase in the grafted animals, whereas swimming in temperate water (25-30°C; 15 min) induced no detectable changes in serotonin output in any of the groups. 5-HIAA levels remained unchanged during forced immobilization, but were significantly reduced during the swimming session in both the intact (-38%) and grafted (-15%) animals. The present results indicate that median raphe grafts can become functionally integrated in the denervated host hippocampus and respond by altered indole output when the animal is exposed to different types of environmental challenges. © 2000 Academic Press.</p>},
  author       = {Cenci, M. A. and Kalén, P.},
  issn         = {0014-4886},
  keyword      = {5-hydroxytryptamine,Functional integration,In vivo microdialysis,Intracerebral neural grafting,Transmitter release,Transplant},
  language     = {eng},
  number       = {2},
  pages        = {351--361},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Serotonin release from mesencephalic raphe neurons grafted to the 5,7-dihydroxytryptamine-lesioned rat hippocampus : Effects of behavioral activation and stress},
  url          = {http://dx.doi.org/10.1006/exnr.2000.7433},
  volume       = {164},
  year         = {2000},
}