Fachbereich Veterinärmedizin



    Behavioural and pharmacological examinations in a transgenic mouse model of early-onset torsion dystonia (2011)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Lange, Nikola
    Hamann, Melanie
    Shashidharan, Pullani
    Richter, Angelika
    Pharmacology, biochemistry, and behavior; 97(4) — S. 647–655
    ISSN: 0091-3057
    DOI: 10.1016/j.pbb.2010.11.005
    Pubmed: 21078339
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
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    Abstract / Zusammenfassung

    Early-onset torsion dystonia is an autosomal dominant movement disorder associated with the DYT1 gene (TOR1A) defect which results in a deletion of a glutamic acid residue in the protein torsinA. The pathophysiology of dystonia is poorly understood. Well characterized animal models can help to give insights into the underlying mechanisms and thereby to develop new therapeutics. In the present study, we further characterized transgenic DYT1 mice, which were initially described to exhibit "dystonia-like" postures. In the present study, several behavioural tests in untreated animals did not show strong differences between transgenic and control mice, but nearly all transgenic mice showed "dystonia-like" postures. However, these movements, also observed in control mice, have to be regarded as a clasping reflex. Since dystonia is thought to be related to dopaminergic dysfunctions, pharmacological investigations have been performed to clarify if dopaminergic substances alter motor behaviour in transgenic mice. Chronic treatment with L-DOPA (combined with carbidopa) enhanced the hindlimb claspings only in transgenic mice, while acute applications of drugs, which exert more selective effects on the dopaminergic system, caused similar reactions in transgenic mice and control mice. Therefore, these data do not provide clear evidence for dysfunctions of the dopaminergic system in this mouse model.