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    Effects of intrastriatal injections of glutamate receptor antagonists on the severity of paroxysmal dystonia in the dtsz mutant (2007)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Sander, Svenja Esther
    Richter, Angelika
    Quelle
    European journal of pharmacology; 563(1-3) — S. 102–108
    ISSN: 0014-2999
    Sprache
    Englisch
    Verweise
    Pubmed: 17349621
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221
    pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Imbalances of the glutamatergic system are implicated in the pathophysiology of various basal ganglia disorders, but few is known about their role in dystonia, a common neurological syndrome in which involuntary muscle co-contractions lead to twisting movements and abnormal postures. Previous systemic administrations of glutamate receptor antagonists in dtsz hamsters, an animal model of primary paroxysmal dystonia, exerted antidystonic effects and electrophysiological experiments pointed to an enhanced corticostriatal glutamatergic activity. In order to examine the pathophysiological relevance of these findings, we performed striatal microinjections of the alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor antagonist 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) and the N-methyl-D-aspartate (NMDA) receptor antagonists D(-)-2-amino-5-phosphopentanoic acid (AP-5), (R)-(+)-3-amino-1-hydroxypyrrolidin-2-one (HA-966) and dizocilpine (MK-801). The striatal application of NBQX reduced the severity and increased the latency to onset of dystonia significantly only at a dosage of 0.08 microg per hemisphere, lower (0.03 microg) and higher dosages (0.16 microg and 0.32 microg) failed to exert comparable effects on the severity. None of the striatal injected NMDA receptor antagonists influenced the severity of the dystonic attacks in the mutant hamster. The combined application of NBQX (0.08 microg) with AP-5 (1.0 microg) failed to exert synergistic antidystonic effects, but the beneficial effect on the severity of dystonia of the single application of NBQX was reproduced. Therefore, corticostriatal glutamatergic overactivity mediated by AMPA receptors, but not by NMDA receptors, is possibly important for the manifestation of dystonic attacks in the dtsz hamster mutant.