Histamine H3 receptor activation inhibits dopamine synthesis but not release or uptake in rat nucleus accumbens

Aquino-Miranda, Guillermo; Escamilla-Sánchez, Juan; González-Pantoja, Raúl; Bueno-Nava, Antonio; Arias‐Montaño, José‐Antonio

doi:10.1016/j.neuropharm.2015.07.006

Cited by 18 publications

(11 citation statements)

References 51 publications

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“…In an earlier study, Schlicker et al (1993) demonstrated that histamine causes a discrete reduction of electrically-evoked [ 3 H]dopamine release from mouse striatal slices, an effect mimicked by α-methylhistamine and blocked by thioperamide at the same concentrations of those used here. Subsequent studies indicated that histamine H3 receptors fail to affect baseline levels of dopamine (Fox et al, 2005;Giannoni et al, 2010;Aquino-Miranda et al, 2015), but reliably modulate extracellular dopamine elevations evoked by pharmacological stimuli (Munzar et al, 2004;Nowak et al, 2008;Alfaro-Rodriguez et al, 2013). In addition, H3 receptors have been shown to modulate behaviors typically regulated by dopaminergic neurotransmission, such as alcohol consumption reinstatement (Nuutinen et al, 2015), alcohol-mediated reward (Nuutinen et al, 2011;Morais-Silva et al, 2016), amphetamine self-administration (Munzar et al, 2004), amphetamine-induced locomotor activity (Munzar et al, 2004;Banks et al, 2009), apomorphine-induced turning behavior in mice with unilateral striatal ablation (Garcia-Ramirez et al, 2004), among others.…”

Section: Discussionmentioning

confidence: 99%

“…Elsewhere in the brain histamine H3 receptors have a well described role as pre-synaptic autoreceptors and heteroreceptors, modulating release of not only histamine (Arrang et al, 1985), but also glutamate (Brown and Haas, 1999), GABA (Yamamoto et al, 1997), serotonin (Threlfell et al, 2004) and acetylcholine (Clapham and Kilpatrick, 1992), among others. However, to date, studies that investigated the effects of histamine H3 receptors on dopamine release have generated conflicting data, indicating either no modulation (Fox et al, 2005;Giannoni et al, 2010;Aquino-Miranda et al, 2015), or decreased dopamine release upon activation of H3 receptors (Schlicker et al, 1993). This could be due to regional differences in the effect of H3 receptors in different parts of the striatum or to the fact that H3 receptors act indirectly to regulate dopamine release, something that could be missed depending on the methods used.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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Histamine H receptors are widely distributed G-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 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 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H receptors affected optogenetically evoked dopamine overflow, indicating that direct H-modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H receptors by α-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 α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…The suspension was subsequently centrifuged at 20 000 g , 4 ° C, for 5 min, and the pellet resuspended and diluted in Krebs assay buffer to 5 mg/mL [method modified from (Westphalen and Hemmings ; Aquino‐Miranda et al . )]. The resulting synaptic membranes no longer enclose an intrasynaptosomal space.…”

Section: Methodsmentioning

confidence: 99%

Lack of evidence for synaptic high‐affinity γ‐hydroxybutyric acid (GHB) transport in rat brain synaptosomes and 11 Na⁺‐dependent SLC neurotransmitter transporters

Thiesen

Frølund

Wellendorph

2019

Journal of Neurochemistry

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γ‐Hydroxybutyric acid (GHB) is an endogenous compound proposed to act as a neurotransmitter. Na+‐dependent, high‐affinity GHB transport has long been considered important evidence supporting this hypothesis. However, the molecular identity of such a high‐affinity transporter remains unknown. In this study, we sought to identify and characterize GHB synaptic transport through a series of studies using both native and recombinant systems with the ultimate aim of providing evidence to clarify the proposed role of GHB as a neurotransmitter in the mammalian brain. Native [3H]GHB transport was studied in isolated rat brain synaptosomes and compared to synaptic membranes. As a targeted approach, GHB was also screened against a panel of Na+‐dependent SLC6 neurotransmitter transporters recombinantly expressed in Xenopus laevis oocytes or tsA201 cells. Finally, the low‐affinity GHB transporters, MCT1/2 and SMCT1, were probed as GHB transporters in L‐[14C]lactate uptake assays in synaptosomes. We found no evidence of high‐affinity [3H]GHB transport in purified rat brain cortical or striatal synaptosomes or at any of the 11 SLC6 transporters tested. Instead, our results indicate the binding of [3H]GHB to an unidentified membrane component, distinct from any of the known GHB targets. In accordance with others, we found that GHB and the analog 3‐hydroxycyclopent‐1‐enecarboxylic acid (HOCPCA) can, in millimolar concentrations, inhibit L‐[14C]lactate uptake at MCT1 and/or MCT2 and that this also can occur in synaptosomes. In conclusion, through a variety of in vitro pharmacological studies, we were unsuccessful in identifying a specific synaptic high‐affinity transporter for GHB. Our findings emphasize the need to reevaluate GHB's role as a potential neurotransmitter. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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“…The location of the H 3 receptor in many aminergic neurons allows its release from terminals to be directly regulated by histamine and H 3 receptor ligands (for a review, see Panula & Nuutinen, 2013). Although in vitro evidence suggests that histamine inhibits the electrically‐evoked release of [ 3 H] dopamine from striatal slices in a manner that is abolished by the H 3 receptor antagonist thioperamide and thus may suggest the presence of presynaptic H 3 receptors on striatal dopaminergic terminals (Schlicker, Fink, Detzner, & Gothert, 1993), in vivo microdialysis has not revealed an evidence of dopamine release in the striatum by H 3 receptor antagonists (Aquino‐Miranda, Escamilla‐Sanchez, Gonzalez‐Pantoja, Bueno‐Nava, & Arias‐Montano, 2016; Nuutinen et al, 2016). The H 3 receptor antagonist GSK189254 did not evoke the release of dopamine in the NAcc (Giannoni et al, 2010), and ABT‐239 , another H 3 receptor antagonist, induced the release of dopamine in the cortex but not the striatum (Fox et al, 2005).…”

Section: Alcohol and Histamine–dopamine Interactionsmentioning

confidence: 99%

Histamine, histamine H₃ receptor, and alcohol use disorder

Panula

2019

British J Pharmacology

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Alcohol use disorder is associated with several mental, physical, and social problems. Its treatment is difficult and often requires a combination of pharmacological and behavioural therapy. The brain histaminergic system, one of the wake‐active systems that controls whole‐brain activity, operates through three neuronal GPCRs. The histamine H3 receptor (Hrh3), which is expressed in many brain areas involved in alcohol drinking and alcohol reward, can be targeted with a number of drugs developed initially for cognitive disorders and/or disorders related to sleep, wakefulness, and alertness. In all rodent alcohol drinking models tested so far, H3 receptor antagonists have reduced alcohol drinking and alcohol‐induced place preference and cue‐induced alcohol reinstatement. Several H3 receptor antagonists tested and found to be safe for humans could be subjected to clinical tests to treat alcohol use disorder. Preference should be given to short‐acting drugs to avoid the sleep problems associated with the wake‐maintaining effects of the drugs. Linked Articles This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc

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Histamine H3 receptor activation inhibits dopamine synthesis but not release or uptake in rat nucleus accumbens

Cited by 18 publications

References 51 publications

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

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

Lack of evidence for synaptic high‐affinity γ‐hydroxybutyric acid (GHB) transport in rat brain synaptosomes and 11 Na⁺‐dependent SLC neurotransmitter transporters

Histamine, histamine H₃ receptor, and alcohol use disorder

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Histamine H3 receptor activation inhibits dopamine synthesis but not release or uptake in rat nucleus accumbens

Cited by 18 publications

References 51 publications

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

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

Lack of evidence for synaptic high‐affinity γ‐hydroxybutyric acid (GHB) transport in rat brain synaptosomes and 11 Na+‐dependent SLC neurotransmitter transporters

Histamine, histamine H3 receptor, and alcohol use disorder

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Product

Resources

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Lack of evidence for synaptic high‐affinity γ‐hydroxybutyric acid (GHB) transport in rat brain synaptosomes and 11 Na⁺‐dependent SLC neurotransmitter transporters

Histamine, histamine H₃ receptor, and alcohol use disorder