Histaminergic ligands improve vestibular compensation in the cat: Behavioural, neurochemical and molecular evidence

This study analysed the effects of betahistine and thioperamide, two histamine H3 receptor antagonists, on the recovery process after unilateral vestibular neurectomy (UVN) in the cat. In UVN animals untreated or treated with betahistine or thioperamide, recovery was evaluated by recording the horizontal spontaneous nystagmus and the postural and locomotor performances. The neurochemical effects of these drugs were determined by examining their impact on the histaminergic system. We quantified the mRNA coding for histidine decarboxylase (enzyme synthesizing histamine) by in situ hybridisation in the tuberomammillary nuclei, while binding density to histamine H3 receptors was assessed using a histamine H3 receptor agonist ([3H]N-α-methylhistamine) and autoradiography methods in the tuberomammillary and the vestibular nuclei. Relative to the UVN-untreated group, cats treated with betahistine or thioperamide showed strongly accelerated behavioural recovery. UVN-induced 1) an up-regulation of histidine decarboxylase mRNA in the tuberomammillary nuclei, strongly accentuated under betahistine and thioperamide, 2) a reduction of the binding to histamine H3 receptors in the vestibular and tuberomammillary nuclei, also strongly enhanced in both groups of treated cats. This study demonstrates that betahistine and thioperamide strongly improve the recovery of vestibular functions in UVN cats by interacting with the histaminergic system.