NeuropharmacologyResearch PaperPharmacological and autoradiographic studies on the pathophysiological role of GABAB receptors in the dystonic hamster: pronounced antidystonic effects of baclofen after striatal injections
Section snippets
Experimental procedures
All experiments were performed in accordance with the European Communities Council Directive (86/609/EEC) and in compliance with the German Animal Welfare Act (G 0160/05). Maximum care was taken to minimize the number of animals used and to minimize their suffering.
Pharmacological examinations
Systemic administration of the GABABR agonist baclofen reduced the severity of dystonic attacks in the hamster mutant during the 3 h of observation at all tested doses (1.5, 2.5 and 3.5 mg/kg; see Fig. 2). All animals which received the higher doses (2.5 or 3.5 mg/kg, respectively) developed a maximum stage of 3 after drug administration. The latency to onset of dystonic movements was increased after the application of 1.5 and 2.5 mg/kg baclofen (see Table 1). Systemic administration of
Discussion
Systemic application of baclofen produced a conclusive antidystonic effect in the dtsz hamster. In contrast to patients with dystonia, where baclofen often has to be administered intrathecally because of adverse reactions, the antidystonic effects in the hamster mutant were achieved at doses which did not provoke marked side effects. Furthermore, beneficial effects lasted longer than the adverse effects. Baclofen is known to pass only poorly through the blood–brain barrier in patients, but this
Conclusion
In summary, the beneficial effect of baclofen which is known from dystonic patients was reproduced in our animal model of paroxysmal dystonia. As indicated by microinjections, striatal mechanisms seem to contribute to the antidystonic action of baclofen. However, our autoradiographic studies do not support the hypothesis of a primary role of GABABRs in the pathophysiology of dystonia in the dtsz hamster. The strong antidystonic effect after striatal microinjection of baclofen is therefore
Acknowledgments
The study was supported by grants from the Deutsche Forschungsgemeinschaft (Ri 845-1-3). We thank A. Russ for his helpful assistance and G. Arndt for her professional support in the statistical analysis of the data.
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