title: Flibanserin attenuates L: -DOPA-sensitized contraversive circling in the unilaterally 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
abstract: 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-HT(1A) 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-HT(1A) 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 (12.5 mg/kg) and benserazide (3.25 mg/kg) for 21 days (on days 1, 3, 5, 8, 11, 14, 17 and 21). On day 24, L: -DOPA-sensitized rats were treated ip 5 min prior to administration of L: -DOPA methyl ester and benserazide with either saline (controls), 2.5, 5 and 10 mg/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 5 mg/kg buspirone and 10 mg/kg flibanserin. The current preclinical findings further implicate the 5-HT(1A) 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.
authors.affiliation: Laboratory for Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany. manfred.gerlach@uni-wuerzburg.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Gerlach
authors.forename: Jürgen
authors.initials: J
authors.lastname: Beck
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001562:Benzimidazoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality / Q000187:drug effects*; D007980:Levodopa / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019956:Stereotypic Movement Disorder / Q000139:chemically induced* / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D001562:Benzimidazoles; C098107:flibanserin; D007980:Levodopa; D016627:Oxidopamine