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Amphetamine-induced abnormal movements occur independently of both transplant- and host-derived serotonin innervation following neural grafting in a rat model of Parkinson's disease.

Lane, Emma LU ; Brundin, Patrik LU and Cenci Nilsson, Angela LU (2009) In Neurobiology of Disease 35. p.42-51
Abstract
Serotonin has been postulated to play a role in the transplant-induced involuntary movements that occur following intrastriatal grafts of ventral mesencephalic tissue in the treatment of Parkinson's disease. Serotonin innervation of the striatum may be derived from either the donor graft tissue or the normal host projections from the midbrain. In two sets of experiments we study the impact of graft- versus host-derived serotonin innervation. All experiments were performed in l-DOPA treated rats with unilateral 6-hydroxydopamine lesions. As expected, following intrastriatal transplantation of embryonic ventral mesencephalon all the transplanted rats exhibited pronounced contralateral rotation in response to amphetamine and some animals also... (More)
Serotonin has been postulated to play a role in the transplant-induced involuntary movements that occur following intrastriatal grafts of ventral mesencephalic tissue in the treatment of Parkinson's disease. Serotonin innervation of the striatum may be derived from either the donor graft tissue or the normal host projections from the midbrain. In two sets of experiments we study the impact of graft- versus host-derived serotonin innervation. All experiments were performed in l-DOPA treated rats with unilateral 6-hydroxydopamine lesions. As expected, following intrastriatal transplantation of embryonic ventral mesencephalon all the transplanted rats exhibited pronounced contralateral rotation in response to amphetamine and some animals also showed severe abnormal involuntary movements (AIMs). In the first set of experiments, all types of AIMs (axial, limb, orolingual and locomotor) were markedly reduced when amphetamine was co-administered with either the D(2) dopamine receptor antagonist raclopride or the D(1) receptor antagonist SCH23390. Cotreatment with the 5-HT(1A) agonist 8-OH-DPAT significantly attenuated the amphetamine-induced axial and limb dyskinesias, whilst locomotor scores remained unchanged. These data point to a major role for dopamine receptors, and to a modulatory role for 5-HT(1A) receptors, in post-grafting dyskinesias. In the second experiment, grafted rats exhibiting amphetamine-induced dyskinesia were subjected to 5,7-dihydroxytryptamine injections into the midbrain in order to destroy the host serotonin innervation. This intervention had no effect on either amphetamine-induced AIMs or contralateral rotation. Histological examination of all grafted rats showed similar numbers of dopaminergic neurons and a very low number of serotonin neurons within the transplants, regardless of AIMs expression. Our results suggest that amphetamine-induced AIMs in grafted animals primarily depend on an activation of dopamine receptors, and that serotonin neurons within either the grafts or the host brain play a negligible role. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurobiology of Disease
volume
35
pages
42 - 51
publisher
Elsevier
external identifiers
  • wos:000267095600006
  • pmid:19361557
  • scopus:67349211457
ISSN
0969-9961
DOI
10.1016/j.nbd.2009.03.014
language
English
LU publication?
yes
id
586e6c87-755f-4352-bbe5-7f2cfbb71cbd (old id 1392196)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19361557?dopt=Abstract
date added to LUP
2009-05-06 13:15:47
date last changed
2017-01-08 05:22:15
@article{586e6c87-755f-4352-bbe5-7f2cfbb71cbd,
  abstract     = {Serotonin has been postulated to play a role in the transplant-induced involuntary movements that occur following intrastriatal grafts of ventral mesencephalic tissue in the treatment of Parkinson's disease. Serotonin innervation of the striatum may be derived from either the donor graft tissue or the normal host projections from the midbrain. In two sets of experiments we study the impact of graft- versus host-derived serotonin innervation. All experiments were performed in l-DOPA treated rats with unilateral 6-hydroxydopamine lesions. As expected, following intrastriatal transplantation of embryonic ventral mesencephalon all the transplanted rats exhibited pronounced contralateral rotation in response to amphetamine and some animals also showed severe abnormal involuntary movements (AIMs). In the first set of experiments, all types of AIMs (axial, limb, orolingual and locomotor) were markedly reduced when amphetamine was co-administered with either the D(2) dopamine receptor antagonist raclopride or the D(1) receptor antagonist SCH23390. Cotreatment with the 5-HT(1A) agonist 8-OH-DPAT significantly attenuated the amphetamine-induced axial and limb dyskinesias, whilst locomotor scores remained unchanged. These data point to a major role for dopamine receptors, and to a modulatory role for 5-HT(1A) receptors, in post-grafting dyskinesias. In the second experiment, grafted rats exhibiting amphetamine-induced dyskinesia were subjected to 5,7-dihydroxytryptamine injections into the midbrain in order to destroy the host serotonin innervation. This intervention had no effect on either amphetamine-induced AIMs or contralateral rotation. Histological examination of all grafted rats showed similar numbers of dopaminergic neurons and a very low number of serotonin neurons within the transplants, regardless of AIMs expression. Our results suggest that amphetamine-induced AIMs in grafted animals primarily depend on an activation of dopamine receptors, and that serotonin neurons within either the grafts or the host brain play a negligible role.},
  author       = {Lane, Emma and Brundin, Patrik and Cenci Nilsson, Angela},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {42--51},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Amphetamine-induced abnormal movements occur independently of both transplant- and host-derived serotonin innervation following neural grafting in a rat model of Parkinson's disease.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2009.03.014},
  volume       = {35},
  year         = {2009},
}