| Abstract | Parkinson's disease (PD) is characterized by the bilateral degeneration of the midbrain dopamine-containing neurons with the most severe lesion in the posterolateral part of the substantia nigra pars compacta (SNpc). In humans, such lesions lead to specific motor abnormalities (i.e., akinesia, rigidity, and tremor) that are greatly improved by levodopa treatment. After a few years, the beneficial effect of the treatment is frequently offset by the development of dyskinesias. To improve treatment strategies, an animal model showing most of the histological and clinical characteristics of the human disease is mandatory. Ten rats received a bilateral injection of small doses of 6-OHDA in the medial forebrain bundle (MFB) and were compared with five sham-lesioned rats. The 6-OHDA-lesioned rats progressively developed abnormal motor behavior (assessed by the stepping test) compared with the sham-lesioned rats. The lesioned rats greatly improved under levodopa treatment, but developed concomitant dyskinesias. All 6-OHDA-lesioned animals had bilateral partial lesions of the SNpc, with the most severe lesion being in its posterolateral part. There was a significant correlation between the severity of the dopaminergic cell loss and the severity of the levodopa-induced dyskinesias. These rats constitute an interesting model of PD, sharing some of the main characteristics of the human disease. |
| Authors | Vincent Paillé, Vincent Henry, Laurent Lescaudron, Philippe Brachet, Philippe Damier
(Affiliation: INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France.)
|
| Journal | Movement disorders : official journal of the Movement Disorder Society
(Mov Disord)
Vol. 22
Issue 4
Pg. 533-9
(Mar 15 2007)
ISSN: 0885-3185 United States |
| PMID | 17230470
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Copyright | (c) 2006 Movement Disorder Society. |
| Chemical References |
- Antiparkinson Agents
- Levodopa
- Dopamine
- Tyrosine 3-Monooxygenase
|
| Topics |
- Animals
- Antiparkinson Agents
(therapeutic use)
- Disease Models, Animal
- Disease Progression
- Dopamine
(metabolism)
- Dyskinesias
(diagnosis, drug therapy, physiopathology)
- Extremities
(physiopathology)
- Levodopa
(therapeutic use)
- Male
- Mesencephalon
(metabolism, pathology)
- Nerve Degeneration
(metabolism, pathology, physiopathology)
- Parkinson Disease
(drug therapy, pathology, physiopathology)
- Prosencephalon
(metabolism, pathology)
- Rats
- Rats, Sprague-Dawley
- Severity of Illness Index
- Substantia Nigra
(metabolism, pathology)
- Tyrosine 3-Monooxygenase
(metabolism)
|
