caa a22 4500 445376619 CHVBK 20180317143004.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00702-010-0571-8 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0571-8 Role of dopamine D3 and serotonin 5-HT1A receptors in l -DOPA-induced dyskinesias and effects of sarizotan in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease [Elektronische Daten] [Manfred Gerlach, Gerd Bartoszyk, Peter Riederer, Olivia Dean, Maarten van den Buuse] Sarizotan, a 5-HT1A agonist with additional affinity for D3 and D4 receptors, has been demonstrated to have anti-dyskinetic effects. The mechanism by which these effects occur is not clear. Using unilateral 6-hydroxydopamine-lesioned rats that received chronic intraperitoneal (ip) administration of l-3,4-dihydroxyphenylalanine (l-DOPA) we investigated the involvement of D3 and 5-HT1A receptors in the effects of sarizotan on contraversive circling and abnormal involuntary movements (AIMs). Before sensitization by chronic l-DOPA treatment (12.5 with 3.25mg/kg benserazide ip, twice daily for 21days), no effect of the selective D3 agonist, PD128907 (1 or 3mg/kg ip), or the selective D3 antagonist, GR103691 (0.5 or 1.5mg/kg ip), was observed. Treatment with sarizotan (1 or 5mg/kg ip) dose-dependently inhibited the l-DOPA-induced contraversive turning and AIMs. In co-treatment with the 5-HT1A antagonist, WAY100635 (1mg/kg ip), sarizotan failed to affect this behaviour, confirming the prominent 5-HT1A receptor-mediated mechanism of action. In the presence of PD128907 (3mg/kg ip), the effects of sarizotan on contraversive turning, locomotive dyskinesia and axial dystonia, but not on orolingual and forelimb dyskinesia, were blocked. On its own, PD128907 had no effect on the behavioural effects of l-DOPA except that it tended to reduce orolingual and forelimb dyskinesia. GR103691 had no effect on its own or in combination with sarizotan. These data identify an involvement of D3 receptors in the action of sarizotan on some, but not all l-DOPA-induced motor side effects. This selective involvement is in contrast to the more general involvement of 5-HT1A receptors in the anti-dyskinetic effects of sarizotan. Springer-Verlag, 2011 l -DOPA-induced dyskinesia nationallicence Abnormal involuntary movements nationallicence Sarizotan nationallicence Parkinson therapy nationallicence Dopamine D3 receptors nationallicence Serotonin 5-HT1A receptors nationallicence AIMs : Abnormal involuntary movements nationallicence ip : Intraperitoneally and introperitoneal, respectively 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 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Laboratory for Clinical Neurobiology, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany aut Bartoszyk Gerd Extended Profiling, Medical Science and Innovation, Merck Serono Research and Development, Frankfurter Strasse 250, 64293, Darmstadt, 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 Dean Olivia Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, 3052, Parkville, VIC, Australia 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), 1733-1742 0300-9564 118:12<1733 2011 118 702 https://doi.org/10.1007/s00702-010-0571-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0571-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gerlach Manfred Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Laboratory for Clinical Neurobiology, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany aut NATIONALLICENCE 700 1- Bartoszyk Gerd Extended Profiling, Medical Science and Innovation, Merck Serono Research and Development, Frankfurter Strasse 250, 64293, Darmstadt, 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- Dean Olivia Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, 3052, Parkville, VIC, Australia 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), 1733-1742 0300-9564 118:12<1733 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer