Abstract

Drugs interfering with the histaminergic system facilitate behavioral recovery after vestibular lesion, likely by increasing histamine turnover and release. The effects of betahistine (structural analogue of histamine) on the histaminergic system were tested by quantifying messenger RNA for histidine decarboxylase (enzyme synthesizing histamine) by in situ hybridization and binding to histamine H(3) receptors (mediating, namely, histamine autoinhibition) using a histamine H(3) receptor agonist ([(3)H]N-alpha-methylhistamine) and radioautography methods. Experiments were done in brain sections of control cats (N=6) and cats treated with betahistine for 1 (N=6) or 3 (N=6) weeks. Betahistine treatment induced symmetrical changes with up-regulation of histidine decarboxylase mRNA in the tuberomammillary nucleus and reduction of [(3)H]N-alpha-methylhistamine labeling in both the tuberomammillary nucleus, the vestibular nuclei complex and nuclei of the inferior olive. These findings suggest that betahistine upregulates histamine turnover and release, very likely by blocking presynaptic histamine H(3) receptors, and induces histamine H(3) receptor downregulation. This action on the histaminergic system could explain the effectiveness of betahistine in the treatment of vertigo and vestibular disease.