Histamine H-3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons

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Varaschin , R K , Osterstock , G , Ducrot , C , Leino , S , Bourque , M-J , Prado , M A M , Prado , V F , Salminen , O , Rannanpää (Nee Nuutinen) , S & Trudeau , L-E 2018 , ' Histamine H-3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons ' , Neuroscience , vol. 376 , pp. 188-203 . https://doi.org/10.1016/j.neuroscience.2018.01.027

Title: Histamine H-3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons
Author: Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josee; Prado, Marco A. M.; Prado, Vania Ferreira; Salminen, Outi; Rannanpää (Nee Nuutinen), Saara; Trudeau, Louis-Eric
Contributor organization: Regenerative pharmacology group
Faculty of Pharmacy
Division of Pharmacology and Pharmacotherapy
Outi Salminen / Principal Investigator
Drug Research Program
DAPHNE - Developing Assessment Practices in Higher Education
Teachers' Academy
Date: 2018-04-15
Language: eng
Number of pages: 16
Belongs to series: Neuroscience
ISSN: 0306-4522
DOI: https://doi.org/10.1016/j.neuroscience.2018.01.027
URI: http://hdl.handle.net/10138/308732
Abstract: Histamine H-3 receptors are widely distributed Gi-coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H-3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H-3 agonist alpha-methylhistamine significantly reduced electrically-evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-beta-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H-3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H-3-modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H-3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H-3 receptors by alpha-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by alpha-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by alpha-methylhistamine. Together, these results indicate that histamine H-3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
Subject: Histamine
H-3 receptor
cholinergic neurons
3112 Neurosciences
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion

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