Abstract

The histaminergic neuronal system and three types of histamine receptors, H₁, H₂ and H₃ 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 H₁ antagonists have been clinically used for the treatment of vertigo or motion sickness and recently, betahistine, a weak H₁ agonist with a potent H₃ 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 H₂ receptors. However, in vitro applications of histamine caused membrane depolarization and increased the firing rate via H₂ 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. H₃ ligands including betahistine are expected to be a promising drug both in the clinical and the laboratory research of the vestibular pathophysiology.