Histamine H-3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons
| Autor: | Sakari Leino, Outi Salminen, Louis-Eric Trudeau, Charles Ducrot, Saara Rannanpää, Marie-Josée Bourque, Vania F. Prado, Marco A. M. Prado, Rafael K. Varaschin, Guillaume Osterstock |
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| Přispěvatelé: | 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Interneuron H3 RECEPTOR striatum NUCLEUS-ACCUMBENS Nucleus accumbens RAT-BRAIN H-3 receptor Cell and Developmental Biology 03 medical and health sciences 0302 clinical medicine Dopamine medicine Cholinergic neuron optogenetics GLUTAMATE RELEASE MOUSE-BRAIN Chemistry General Neuroscience AUTORADIOGRAPHIC LOCALIZATION Dopaminergic 3112 Neurosciences Histamine dopamine cholinergic neurons Nicotinic acetylcholine receptor 030104 developmental biology medicine.anatomical_structure SYNAPTIC-TRANSMISSION nervous system AGONIST IMMEPIP Cholinergic Anatomy Histamine H3 receptor Neuroscience 030217 neurology & neurosurgery H-3-RECEPTOR LIGANDS medicine.drug CAUDATE-PUTAMEN |
| Zdroj: | Anatomy and Cell Biology Publications |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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