Fachbereich Veterinärmedizin



    Autoradiography of central GABAB receptors in an animal model of paroxysmal dystonia (2007)

    Sander, S. E.
    Nobrega, J. N.
    Raymond, R.
    Richter, A.
    48th Spring Meeting Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie
    Mainz, 13. – 15.03.2007
    Naunyn-Schmiedeberg´s Archives of Pharmacology; 375(Suppl.1) — S. 55
    ISSN: 0028-1298
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
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    Abstract / Zusammenfassung

    GABAB receptors are widely expressed and distributed in the nervous system and have been
    implicated in a variety of disorders such as epilepsy and spasticity. In dystonia, a movement
    disorder in which muscle co-contractions cause repetitive twisting movements or abnormal
    postures, their pathophysiological role is still unknown. Studies in the dtsz mutant hamster, an
    animal model of primary paroxysmal dystonia, demonstrated alterations of the GABAergic
    system, e.g., an ontogenetically decreased density of striatal GABAergic interneurons and
    changes in GABAA receptor binding in several regions of the CNS. In order to clarify if GABAB
    receptors are also involved in the pathophysiology of dystonia in the hamster mutant, we
    performed quantitative autoradiographic analysis of ligand binding to the selective GABAB
    receptor antagonist [3H]-CGP54626. In the dtsz hamster, dystonia is stress-inducible and occurs
    between the 16th and 70th day of life. Ten dtsz hamsters were decapitated at the age of maximum
    expression of dystonic attacks (34-36 d) together with an age- and gender-matched control
    group without preceding induction of dystonia. The brains were removed, immediately frozen
    and sliced at a temperature of -20°C. The slices were incubated with 2 nM [3H]-CGP54626 and
    in order to define non-specific binding 10 μM CGP55845 was used. Densitometric analysis was
    performed with the MCID system. In none of the examined 32 brain regions was a significant
    difference (Bonferroni-corrected: p<0.0016) detectable between dtsz hamsters and control
    animals. The results of our study propose that GABAB receptors are not altered under basal
    conditions in the dtsz hamster. Further studies, including intrastriatal applications of GABAB
    receptor modulators, have to clarify the role of GABAB receptors in the manifestation of dystonic
    This work was supported by DFG grant Ri 845/1-2.