Betahistine Dihydrochloride Treatment Facilitates Vestibular Compensation in the Cat

Abstract

Unilateral lesion of the vestibular system induces posturo-locomotor deficits that are compensated for with time. Drug therapy is currently used to improve the recovery process and to facilitate vestibular compensation. Betahistine dihydrochloride is an histamine-like substance that has been employed in vestibular pathology; it was found effective in many forms of vertigo and in vestibular-related syndromes. Investigations performed in animal models have shown betahistine-induced neuronal modulations in the vestibular nuclei complex and interactions with the H1 and H3 histamine receptors. Potentially, this substance is therefore capable to interfere with some recovery mechanisms and to improve the behavioral adaptations. But there is at present a total lack of data concerning the influence of betahistine treatment on vestibular compensation in animal models. The aim of this study was to understand the pharmacological activity of betahistine in the restoration of posture and locomotor balance functions in unilateral vestibular neurectomized cats. Posture recovery was assessed by quantifying the surface reaction of the cat's support as measured while standing erect on its four legs, at rest. Locomotor balance recovery was determined using the rotating beam test, by measuring the maximal performance (max. P.) of the cat and its locomotion speed regulation during the postoperative time period. We have compared the recovery profile and time course of these static (posture) and dynamic (equilibrium) functions in three groups of cats. Two experimental groups were treated at daily doses of 50 mg/kg and 100 mg/kg, respectively. Betahistine dihydrochloride was given orally until complete recovery of posturolocomotor functions. One untreated control group served as the reference. Results showed that postoperative treatment strongly accelerated the recovery process in both treated groups, inducing a time benefit of around 2 weeks as compared to the controls. Maximum performance of the cats on the rotating beam as well as locomotion speed regulation were highly correlated to the postoperative development of the cat's support surface, indicating that compensation of the static vestibulospinal deficits conditioned the subsequent locomotor balance recovery. These behavioral data showed that betahistine dihydrochloride constitutes a useful drug therapy for the symptomatic treatment of central vestibular disorders in our animal model of unilateral vestibular lesion. Improvement of vestibular compensation under betahistine postoperative treatment, as evidenced here for the posture and locomotor balance functions, is discussed both in terms of aspecific effect (histamine-induced increase of the level of vigilance) or more direct action in the vestibular nuclei (histamine-induced rebalance of neuronal activity on both sides).