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Flibanserin attenuates l-DOPA-sensitized contraversive circling in the unilaterally 6-hydroxydopamine-lesioned rat model of Parkinson’s disease

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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-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 (12.5 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-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.

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Abbreviations

AIMs:

Abnormal involuntary movements

ip:

Intraperitoneally

l-DOPA:

Levodopa, l-3,4-dihydroxyphenylalanine

LID:

l-DOPA-induced dyskinesia

PD:

Parkinson’s disease

5-HT:

Serotonin, 5-hydroxytryptamine

6-OHDA:

6-Hydroxydopamine

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Acknowledgments

This study was funded by Monitoring Force GmbH (Münster, Germany) without any restriction.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory for Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany

    Manfred Gerlach

  2. Monitoring Force GmbH, Bahnhofstrasse 11, 48143, Münster, Germany

    Jürgen Beck

  3. 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

    Peter Riederer

  4. Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, Parkville, VIC, 3052, Australia

    Maarten van den Buuse

Authors
  1. Manfred Gerlach
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  2. Jürgen Beck
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  3. Peter Riederer
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  4. Maarten van den Buuse
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Correspondence to Manfred Gerlach.

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Gerlach, M., Beck, J., Riederer, P. et al. Flibanserin attenuates l-DOPA-sensitized contraversive circling in the unilaterally 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. J Neural Transm 118, 1727–1732 (2011). https://doi.org/10.1007/s00702-010-0570-9

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