Chronic administration of the histamine H3 receptor agonist immepip decreases l-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats

  • Alberto Avila-Luna
  • Camilo Ríos
  • Arturo Gálvez-Rosas
  • Sergio Montes
  • José-Antonio Arias-Montaño
  • Antonio Bueno-NavaEmail author
Original Investigation



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.


Dopamine Histamine D1 receptor H3 receptor Dyskinesia Striatum Parkinson’s disease l-Dopa Immepip 



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.

Supplementary material

Supplementary video 1

Effect of the administration of L-Dopa (6.25 mg/kg) and the co-administration of L-Dopa and the H3R agonist immepip (1 mg/kg) in 6-OHDA-lesioned rats. Note that the administration of immepip reduces LIDs in 6-OHDA-lesioned rats (MP4 38915 kb)

Supplementary video 2

Effects of the chronic administration of immepip+L-Dopa for 14 days, and immepip withdrawal on day 15. Drugs administration was as described for Video 1 (MP4 31326 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alberto Avila-Luna
    • 1
    • 2
  • Camilo Ríos
    • 3
    • 4
  • Arturo Gálvez-Rosas
    • 1
  • Sergio Montes
    • 3
  • José-Antonio Arias-Montaño
    • 5
  • Antonio Bueno-Nava
    • 1
    Email author
  1. 1.Lab. Neurofisiología Química de la Discapacidad, División de NeurocienciasInstituto Nacional de Rehabilitación Luis Guillermo Ibarra IbarraMexico CityMexico
  2. 2.Programa de Doctorado en Ciencias Biológicas y de la SaludUniversidad Autónoma MetropolitanaMexico CityMexico
  3. 3.Departamento de NeuroquímicaInstituto Nacional de Neurología y Neurocirugía Manuel Velasco SuárezMexico CityMexico
  4. 4.Lab. Neurofarmacología Molecular, Departamento de Sistemas BiológicosUniversidad Autónoma MetropolitanaMexico CityMexico
  5. 5.Departamento de Fisiología, Biofísica y NeurocienciasCentro de Investigación y de Estudios Avanzados del IPNMexico CityMexico

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