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Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal

Rafael Koerich Varaschin1, Guillaume Osterstock1, Charles Ducrot1

  • 1Department of Pharmacology and Physiology, Department of Neurosciences, School of Medicine, CNS Research Group, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Neuroscience
|January 29, 2018
PubMed
Summary

Histamine H3 receptor activation reduces dopamine release in the ventral striatum by inhibiting cholinergic interneurons. This finding clarifies the role of H3 receptors in modulating dopamine signaling via indirect pathways.

Keywords:
H(3) receptorHistaminecholinergic neuronsdopamineoptogeneticsstriatum

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Neurochemistry

Background:

  • Histamine H3 receptors (H3Rs) are G-protein coupled receptors that modulate neurotransmitter release.
  • Their role in regulating dopamine (DA) release in the striatum, particularly the ventral striatum, is not fully understood.
  • Cholinergic interneurons are known to influence DA release in the striatum.

Purpose of the Study:

  • To investigate the modulatory role of histamine H3 receptors on activity-dependent dopamine release in the ventral striatum.
  • To determine the specific neuronal populations and mechanisms through which H3Rs affect dopamine overflow.
  • To elucidate the contribution of H3Rs to the regulation of dopaminergic neurotransmission.

Main Methods:

  • Fast-scan cyclic voltammetry was used to measure dopamine transients in acute brain slices.
  • Electrically and optogenetically evoked dopamine overflow was assessed in response to H3 receptor activation.
  • Quantitative PCR (qPCR) was employed to confirm H3 receptor mRNA expression in striatal neurons.
  • Electrophysiological recordings were performed to measure the firing activity of cholinergic interneurons.

Main Results:

  • Activation of histamine H3 receptors by α-methylhistamine significantly reduced electrically-evoked dopamine overflow.
  • This reduction was blocked by a nicotinic acetylcholine receptor antagonist, indicating involvement of cholinergic interneurons.
  • Histamine H3 receptor activation decreased spontaneous firing of cholinergic interneurons in the ventral striatum.
  • Histamine H3 receptor mRNA was confirmed in both ventral and dorsal striatal cholinergic interneurons.

Conclusions:

  • Histamine H3 receptors indirectly diminish dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity.
  • The primary mechanism involves decreased firing of ventral striatal cholinergic interneurons, leading to reduced cholinergic tone on dopaminergic axons.
  • These findings highlight the specific role of H3Rs in modulating dopamine release through cholinergic pathways in the ventral striatum.