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

Abstract

RATIONALE:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Alberto Avila-Luna, Camilo Ríos, Arturo Gálvez-Rosas, Sergio Montes, José-Antonio Arias-Montaño, Antonio Bueno-Nava
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 236 Issue 6 Pg. 1937-1948 (Jun 2019) ISSN: 1432-2072 [Electronic] Germany
• PMID: 30762089 (Publication Type: Journal Article)

Chemical References

• Histamine Agonists
• Imidazoles
• Piperidines
• Receptors, Histamine H3
• 4-(1H-imidazol-4-ylmethyl)piperidine
• Levodopa
• Oxidopamine

Topics

• Animals
• Corpus Striatum (drug effects, metabolism)
• Dyskinesia, Drug-Induced (drug therapy, metabolism)
• Histamine Agonists (administration & dosage)
• Imidazoles (administration & dosage)
• Levodopa (toxicity)
• Male
• Oxidopamine (toxicity)
• Piperidines (administration & dosage)
• Rats
• Rats, Wistar
• Receptors, Histamine H3 (physiology)
• Substantia Nigra (drug effects, metabolism)