Chronic activation of histamine H3 receptors reduces L-dopa-induced dyskinesias in a model of hemiparkinsonian rats with 6-hydroxydopamine lesions

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 H 3 receptors (H 3 Rs) 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 H 3 R agonist immepip.In contrast, withdrawal of immepip restored the dyskinesias induced by chronic L-Dopa treatment.Conclusion: The antidyskinetic effect of H 3 R activation may be explained by the functional interaction between dopamine D1 receptors and H 3 Rs, which are colocalized in the striatum.