Histamine H3 receptors (H3Rs) are co-expressed with dopamine D1 receptors (D1Rs) by striato-nigral medium spiny GABAergic neurons, where they functionally antagonize D1R-mediated responses.
Objectives and methods
We examined whether the chronic administration of the H3R agonist immepip modifies dyskinesias induced by l-3,4-dihydroxyphenylalanine, l-Dopa (LIDs), in rats lesioned with 6-hydroxydopamine in the substantia nigra pars compacta, and the effect of D1R and H3R co-activation on glutamate and GABA content in dialysates from the dorsal striatum of naïve rats.
The systemic administration (i.p.) of l-Dopa for 14 days significantly increased axial, limb, and orolingual abnormal involuntary movements (AIMs) compared with the vehicle group. The chronic administration of the H3R agonist immepip alongside l-Dopa significantly decreased axial, limb, and orolingual AIMs compared with l-Dopa alone, but AIMs returned to previous values on immepip withdrawal. Chronic immepip was ineffective when administered prior to l-Dopa. The chronic administration of immepip significantly decreased GABA and glutamate content in striatal dialysates, whereas the administration of l-Dopa alone increased GABA and glutamate content.
These results indicate that chronic H3R activation reduces LIDs, and the effects on striatal GABA and glutamate release provide evidence for a functional interaction between D1Rs and H3Rs.
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We thank MVZ Hugo Lecona Butrón for the support with housing, care, maintenance, and monitoring of the health of the experimental animals at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra. We thank MVZ Javier Pérez Gallaga for the technical support. The authors wish to thank Dr. Ivonne M. Heuze de Icaza for her support with the experimental animals.
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Avila-Luna, A., Ríos, C., Gálvez-Rosas, A. et al. Chronic administration of the histamine H3 receptor agonist immepip decreases l-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats. Psychopharmacology 236, 1937–1948 (2019). https://doi.org/10.1007/s00213-019-5182-y
- D1 receptor
- H3 receptor
- Parkinson’s disease