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Chronic activation of histamine H3 receptors reduces L-dopa-induced dyskinesias in a model of hemiparkinsonian rats with 6-hydroxydopamine lesions
Chronic activation of histamine H3 receptors reduces L-dopa-induced dyskinesias in a model of hemiparkinsonian rats with 6-hydroxydopamine lesions
Alberto Avila-Luna 1, Antonio Verduzco-Mendoza 2, Silvia A. Olmos-Hernández 2, Adriana Domínguez-Oliva 3, Arturo Gálvez-Rosas 1, José A. Arias-Montaño 4, Antonio Bueno-Nava 1
1 Division of Basic Neuroscience, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Secretaría de Salud, Mexico City, Mexico; 2 Animal Facility and Experimental Surgery, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Secretaría de Salud, Mexico City, Mexico; 3 Department of Agricultural and Animal Production, Universidad Atónoma Metropolitana, Xochimilco Unit, Mexico City, Mexico; 4 Department of Physiology, Biophysics, and Neuroscience, Center for Research and Advanced Studies, Instituto Politécnico Nacional, Mexico City, Mexico
*Correspondence: Antonio Bueno-Nava. Email: abueno@inr.gob.mx
Abstract
Background: Involuntary movements induced by L-3,4-dihydroxyphenylalanine (L-Dopa), known as dyskinesias, are a common side effect associated with long-term L-Dopa administration. Objective: In this study, we examined whether chronic activation of histamine H3 receptors (H3Rs) reduces dyskinesias in 6-hydroxydopamine (6-OHDA)-lesioned rats. Material and methods: 6-OHDA-lesioned rats treated with L-Dopa and the histaminergic agonist immepip were used. Results: Daily intraperitoneal (i.p.) administration of L-Dopa for 14 days increased axial, limb, and orolingual dyskinesias. This effect was attenuated by the coadministration of the H3R agonist immepip. In contrast, withdrawal of immepip restored the dyskinesias induced by chronic L-Dopa treatment. Conclusion: The antidyskinetic effect of H3R activation may be explained by the functional interaction between dopamine D1 receptors and H3Rs, which are colocalized in the striatum.
Keywords: Parkinson’s disease. Dyskinesias. L-Dopa. H3receptor. Rat.
