Histaminergic ligands attenuate barrel rotation in rats following unilateral labyrinthectomy

In this paper we present a unilateral labyrinthectomy (UL) surgical procedure in rats that was derived from previous techniques. The utility of this model to assess vestibular dysfunction was evaluated by examining the ability of clinically used histaminergic agents and more selective H3 receptor antagonists to attenuate of UL-induced body rotations. Unilateral labyrinthectomy was performed by injection of ethanol into the rat right inner ear. An elevated body rotation test (EBRT) was used to assess the abnormal rotational behavior induced by UL. Scores of "3" to "0" were used to characterize the degree of abnormal behavior according to the latency of body rotations to begin. Our results demonstrate that: i) 100 microliters ethanol induced robust behavioral changes, which was used in further experiments; ii) the clinically used antivertigo agent, astemizole, significantly reduced the rotational behavior in UL rats; iii) the more potent H3 antagonists, thioperamide and GT-2016, were more efficacious than betahistine, a mixed H3 antagonist and H1 agonist. These results indicate that this model may be a potential tool for testing novel drugs for antivertigo effects and provide better support to the role of the histaminergic system in the control of vestibular function.