Publikationsdatenbank

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

Art

Poster

Autoren

Sander, S. E.

Nobrega, J. N.

Raymond, R.

Richter, A.

Kongress

48th Spring Meeting Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie

Mainz, 13. – 15.03.2007

Quelle

Naunyn-Schmiedeberg's archives of pharmacology

Bandzählung: 375

Heftzählung: Suppl.1

Seiten: 55

ISSN: 0028-1298

Sprache

Englisch

Kontakt

Institut für Pharmakologie und Toxikologie

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

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
56
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
attacks.
This work was supported by DFG grant Ri 845/1-2.