caa a22 4500 445376643 CHVBK 20180317143004.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00702-010-0570-9 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0570-9 Flibanserin attenuates l -DOPA-sensitized contraversive circling in the unilaterally 6-hydroxydopamine-lesioned rat model of Parkinson's disease [Elektronische Daten] [Manfred Gerlach, Jürgen Beck, Peter Riederer, Maarten van den Buuse] A central problem in the treatment of Parkinson's disease (PD) is the development of motor disturbances like l-DOPA-induced dyskinesia (LID) after long-term treatment. Preclinical and clinical studies demonstrated that serotonin 5-HT1A receptor agonists attenuate this disabling motor side effect. The aim of this study was to investigate the ability of flibanserin compared to buspirone to attenuate l-DOPA-sensitized contraversive circling in hemiparkinsonian rats, which is an animal model of LID. Both drugs have a preferential affinity for the serotonin 5-HT1A receptors. Buspirone was in comparison because it was expected to have an effect in this model. Unilaterally 6-hydroxydopamine lesioned rats were treated twice daily intraperitoneally (ip) with l-DOPA methylester (12.5mg/kg) and benserazide (3.25mg/kg) for 21days (on days 1, 3, 5, 8, 11, 14, 17 and 21). On day 24, l-DOPA-sensitized rats were treated ip 5min prior to administration of l-DOPA methyl ester and benserazide with either saline (controls), 2.5, 5 and 10mg/kg buspirone or flibanserin. Acute administration of both flibanserin and buspirone, dose dependently, attenuated the increased contraversive circling. An almost complete inhibition of the turning response was observed at 5mg/kg buspirone and 10mg/kg flibanserin. The current preclinical findings further implicate the 5-HT1A receptor as a promising therapeutic target for the reduction of LID and predict a potential efficacy of flibanserin in the treatment of LID in PD. Springer-Verlag, 2011 l -DOPA-induced dyskinesia nationallicence Rat nationallicence 6-Hydroxydopamine nationallicence Serotonin 5-HT1A agonists nationallicence Buspirone nationallicence Flibanserin nationallicence Parkinson therapy nationallicence AIMs : Abnormal involuntary movements nationallicence ip : Intraperitoneally nationallicence l -DOPA : Levodopa, l-3,4-dihydroxyphenylalanine nationallicence LID : l-DOPA-induced dyskinesia nationallicence PD : Parkinson's disease nationallicence 5-HT : Serotonin, 5-hydroxytryptamine nationallicence 6-OHDA : 6-Hydroxydopamine nationallicence Gerlach Manfred Laboratory for Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany aut Beck Jürgen Monitoring Force GmbH, Bahnhofstrasse 11, 48143, Münster, Germany aut Riederer Peter Laboratory for Clinical Neurochemistry, Department of Psychiatry, Psychosomatics and Psychotherapy, and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany aut van den Buuse Maarten Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, 3052, Parkville, VIC, Australia aut Journal of Neural Transmission Springer Vienna 118/12(2011-12-01), 1727-1732 0300-9564 118:12<1727 2011 118 702 https://doi.org/10.1007/s00702-010-0570-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0570-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gerlach Manfred Laboratory for Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany aut NATIONALLICENCE 700 1- Beck Jürgen Monitoring Force GmbH, Bahnhofstrasse 11, 48143, Münster, Germany aut NATIONALLICENCE 700 1- Riederer Peter Laboratory for Clinical Neurochemistry, Department of Psychiatry, Psychosomatics and Psychotherapy, and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany aut NATIONALLICENCE 700 1- van den Buuse Maarten Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, 3052, Parkville, VIC, Australia aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/12(2011-12-01), 1727-1732 0300-9564 118:12<1727 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer