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 (12.5mg/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-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.