Advanced

Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat

Kirik, Deniz LU ; Rosenblad, Carl and Björklund, Anders LU (1998) In Experimental Neurology 152(2). p.259-277
Abstract
Partial lesions of the nigrostriatal dopamine system have been investigated with respect to their ability to induce consistent long-lasting deficits in movement initiation and skilled forelimb use. In eight different lesion groups 6-hydroxydopamine (6-OHDA) was injected at one, two, three, or four sites into the lateral sector of the right striatum, in a total dose of 20-30 microgram. Impairments in movement initiation in a forelimb stepping test, and in skilled paw use in a paw-reaching test, was seen only in animals where the severity of the lesion exceeded a critical threshold, which was different for the different tests used: single (1 x 20 microgram) or two-site (2 x 10 microgram) injections into the striatum had only small affects on... (More)
Partial lesions of the nigrostriatal dopamine system have been investigated with respect to their ability to induce consistent long-lasting deficits in movement initiation and skilled forelimb use. In eight different lesion groups 6-hydroxydopamine (6-OHDA) was injected at one, two, three, or four sites into the lateral sector of the right striatum, in a total dose of 20-30 microgram. Impairments in movement initiation in a forelimb stepping test, and in skilled paw use in a paw-reaching test, was seen only in animals where the severity of the lesion exceeded a critical threshold, which was different for the different tests used: single (1 x 20 microgram) or two-site (2 x 10 microgram) injections into the striatum had only small affects on forelimb stepping, no effect on skilled paw use. More pronounced deficits were obtained in animals where the same total dose of 6-OHDA was distributed over three or four sites along the rostro-caudal extent of the lateral striatum or where the injections were made close to the junction of the globus pallidus. The results show that a 60-70% reduction in tyrosine hydroxylase (TH)-positive fiber density in the lateral striatum, accompanied by a 50-60% reduction in TH-positive cells in substantia nigra (SN), is sufficient for the induction of significant impairment in initiation of stepping. Impaired skilled paw-use, on the other hand, was obtained only with a four-site (4 x 7 microgram) lesion, which induced 80-95% reduction in TH fiber density throughout the rostrocaudal extent of the lateral striatum and a 75% loss of TH-positive neurons in SN. Drug-induced rotation, by contrast, was observed also in animals with more restricted presymptomatic lesions. The results indicate that the four-site intrastriatal 6-OHDA lesion may be a relevant model of the neuropathology seen in parkinsonian patients in a manifest symptomatic stage of the disease and may be particularly useful experimentally since it leaves a significant portion of the nigrostriatal projection intact which can serve as a substrate for regeneration and functional recovery in response to growth promoting and neuroprotective agents. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Parkinson's disease, 6-hydroxydopamine, tyrosine hydroxylase, stepping, paw-use, sensorimotor behavior, cell loss, stereology
in
Experimental Neurology
volume
152
issue
2
pages
259 - 277
publisher
Academic Press
external identifiers
  • pmid:9710526
  • scopus:0032143368
ISSN
0014-4886
DOI
10.1006/exnr.1998.6848
language
English
LU publication?
yes
id
2fc8b3f1-1215-4592-a02c-d5c23f06f578 (old id 1113770)
date added to LUP
2008-07-16 11:09:56
date last changed
2017-08-06 03:51:51
@article{2fc8b3f1-1215-4592-a02c-d5c23f06f578,
  abstract     = {Partial lesions of the nigrostriatal dopamine system have been investigated with respect to their ability to induce consistent long-lasting deficits in movement initiation and skilled forelimb use. In eight different lesion groups 6-hydroxydopamine (6-OHDA) was injected at one, two, three, or four sites into the lateral sector of the right striatum, in a total dose of 20-30 microgram. Impairments in movement initiation in a forelimb stepping test, and in skilled paw use in a paw-reaching test, was seen only in animals where the severity of the lesion exceeded a critical threshold, which was different for the different tests used: single (1 x 20 microgram) or two-site (2 x 10 microgram) injections into the striatum had only small affects on forelimb stepping, no effect on skilled paw use. More pronounced deficits were obtained in animals where the same total dose of 6-OHDA was distributed over three or four sites along the rostro-caudal extent of the lateral striatum or where the injections were made close to the junction of the globus pallidus. The results show that a 60-70% reduction in tyrosine hydroxylase (TH)-positive fiber density in the lateral striatum, accompanied by a 50-60% reduction in TH-positive cells in substantia nigra (SN), is sufficient for the induction of significant impairment in initiation of stepping. Impaired skilled paw-use, on the other hand, was obtained only with a four-site (4 x 7 microgram) lesion, which induced 80-95% reduction in TH fiber density throughout the rostrocaudal extent of the lateral striatum and a 75% loss of TH-positive neurons in SN. Drug-induced rotation, by contrast, was observed also in animals with more restricted presymptomatic lesions. The results indicate that the four-site intrastriatal 6-OHDA lesion may be a relevant model of the neuropathology seen in parkinsonian patients in a manifest symptomatic stage of the disease and may be particularly useful experimentally since it leaves a significant portion of the nigrostriatal projection intact which can serve as a substrate for regeneration and functional recovery in response to growth promoting and neuroprotective agents.},
  author       = {Kirik, Deniz and Rosenblad, Carl and Björklund, Anders},
  issn         = {0014-4886},
  keyword      = {Parkinson's disease,6-hydroxydopamine,tyrosine hydroxylase,stepping,paw-use,sensorimotor behavior,cell loss,stereology},
  language     = {eng},
  number       = {2},
  pages        = {259--277},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat},
  url          = {http://dx.doi.org/10.1006/exnr.1998.6848},
  volume       = {152},
  year         = {1998},
}