The histaminergic neuronal system and three types of histamine receptors, H
1, H
2 and H
3 receptors, have been identified in the brain and both histaminergic innerva-tion and the presence of all three histamine receptors have been demonstrated in the vestibular nucleus. Brain-penetrating H
1 antagonists have been clinically used for the treatment of vertigo or motion sickness and recently, betahistine, a weak H
1 agonist with a potent H
3 antagonistic activity, was introduced in the treatment of vertigo, demonstrating the significance of brain histamine in the pathophysiology of vestibular function.
In animal experiments, either unilateral vestibular caloric stimulation or hyper-gravity stimulation activates the histaminergic system, which may promote the symp-toms associated with vertigo or motion sickness such as nausea and vomiting. However, the direct effects of histamine on the neurons in the vestibular nucleus remain con-troversial. In vivo studies reported that the firing rates of most neurons in the vestibu-lar nucleus were decreased by histamine via H
2 receptors. However, in vitro applications of histamine caused membrane depolarization and increased the firing rate via H
2 receptors.
In addition to these direct actions on vestibular neurons, histamine or betahistine increases the cerebral and inner ear blood flows, which may contribute to the therapeu-tic benefit for vertigo. H
3 ligands including betahistine are expected to be a promising drug both in the clinical and the laboratory research of the vestibular pathophysiology.
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