Betahistine, vestibular function and compensation: in vitro studies of vestibular function and plasticity.
Histamine has an excitatory action on rat medial vestibular nucleus neurones in vitro, an effect that is mediated by histamine H1 and H2 receptors. Betahistine, which is a weak agonist at the H1 receptor and a moderate antagonist at the presynaptic H3 autoreceptor, weakly excites medial vestibular nucleus cells but antagonizes their responses to histamine. Experiments were carried out on rat medial vestibular nucleus cells in vitro using slices prepared from animals that had undergone unilateral labyrinthectomy (UL). There was a significant increase in the intrinsic excitability of medial vestibular nucleus cells in the rostral region of the ipsi-lesional nucleus within 4 h post-UL, which was sustained for the following week. These changes in intrinsic excitability of the medial vestibular nucleus neurones were abolished in animals that were not exposed to the secretion of stress hormones that normally occurs following UL. Histamine is also released in response to the stress associated with vestibular dysfunction. It is possible that the beneficial effects of betahistine on vestibular compensation are related to an interaction between histaminergic receptors activated by the parallel release of histamine and the activation of glucocorticoid receptors through the activation of the stress axis. Further study of the interactions between histamine receptors and the activation of the stress axis may be useful in understanding the effects of betahistine on vestibular plasticity.
Dutia
M B
MB
Department of Biomedical Sciences (Physiology), University of Edinburgh, UK. m.b.dutia@ed.ac.uk
D000222:Adaptation, Physiological; D000818:Animals; D001621:Betahistine / Q000494:pharmacology*; D007758:Ear, Inner / Q000601:surgery; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology; D014726:Vestibular Nuclei / Q000187:drug effects* / Q000502:physiology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D001621:Betahistine