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The 5-HT1A-receptor agonist flibanserin reduces drug-induced dyskinesia in RGS9-deficient mice

  • Movement Disorders - Original Article
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Abstract

Drug-induced dyskinesia is a major complication of dopamine replacement therapy in advanced Parkinson’s disease consisting of dystonia, chorea and athetosis. Agonists at 5-HT1A-receptors attenuate levodopa-induced motor complications in non-human primates. Mice with increased dopamine D2 receptor (DRD2) signalling due to the lack of expression of the regulator of G-protein signalling 9 (RGS9) also develop dyskinesia following levodopa treatment. We investigated whether the 5-HT1A-receptor agonist flibanserin compared with buspirone reduces motor abnormalities induced by levodopa or quinelorane, a selective dopamine D2-receptor agonist. Following dopamine depletion via reserpine, 40 mice (20 wild-type and 20 RGS9 knock-out) were treated with flibanserin or buspirone in combination with levodopa or quinelorane. Motor behaviour was analysed using open field analysis. RGS9 knock-out mice displayed significantly more drug-induced dystonia (p < 0.04; t test) than wild type. In quinelorane-treated wild-type mice flibanserin as well as buspirone significantly reduced dystonia (p < 0.05). In RGS9 knock-out animals again both reduced quinelorane-induced dystonia. However, flibanserin was significantly more effective (p = 0.003). Following reserpine pretreatment and administration of levodopa wild-type and RGS 9 knock-out mice showed mild to moderate dystonia. Surprisingly, 10 mg/kg buspirone increased dystonia in both animal groups, whereas it was decreased by 10 mg/kg flibanserin. However, compared with levodopa alone only the increase of dystonia by buspirone was significant (p < 0.04). Flibanserin showed promising antidyskinetic effects in a model of drug-induced dyskinesia. Our data underline the possible benefit of 5-HT1A agonists in drug-induced dyskinesia.

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Authors and Affiliations

  1. NRZ, Neurological Rehabilitation Center, University of Leipzig, Muldentalweg 1, 04828, Bennewitz, Germany

    Karl Strecker & Michael Adamaszek

  2. Department of Neurology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany

    Karl Strecker, Sven Ohm & Johannes Schwarz

  3. Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Florian Wegner

  4. Monitoring Force, Münster, Germany

    Jürgen Beck

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  1. Karl Strecker
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Correspondence to Karl Strecker.

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Strecker, K., Adamaszek, M., Ohm, S. et al. The 5-HT1A-receptor agonist flibanserin reduces drug-induced dyskinesia in RGS9-deficient mice. J Neural Transm 119, 1351–1359 (2012). https://doi.org/10.1007/s00702-012-0815-x

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