Rat model of Parkinson's disease with bilateral motor abnormalities, reversible with levodopa, and dyskinesias

Authors

  • Vincent Paillé PhD,

    1. INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France
    2. UFR de Médecine,Université de Nantes, Nantes, France
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  • Vincent Henry MS,

    1. INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France
    2. UFR de Médecine,Université de Nantes, Nantes, France
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  • Laurent Lescaudron PhD,

    1. INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France
    2. UFR des Sciences et des Techniques,Université de Nantes, Nantes, France
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  • Philippe Brachet PhD,

    1. INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France
    2. UFR de Médecine,Université de Nantes, Nantes, France
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  • Philippe Damier MD, PhD

    Corresponding author
    1. INSERM, UMR 643 and Institut de Transplantation et de Recherche en Transplantation, CHU, Nantes, France
    2. CHU Nantes, Clinique Neurologique and Centre d'Investigation Clinique, Nantes, France
    • Clinique Neurologique, Hôpital Guillaume et René Laënnec, Boulevard Jacques Monod, F-44093 Nantes Cedex 01, France
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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. © 2006 Movement Disorder Society

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