Effects of Betahistine on the Development of Vestibular Compensation after Unilateral Labyrinthectomy in Rats.

Junya Fukuda,Noriaki Takeda,Takahiro Azuma,Yoshiaki Kitamura,Kazunori Matsuda,Koichi Tomita,Go Sato,Momoyo Matsuoka,Tadashi Kitahara

doi:10.3390/brainsci11030360

Abstract

Background: Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC. Objective: We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats. Methods: Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe. Results: The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats. Conclusion: These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.

Highlights

Unilateral vestibular dysfunction causes spontaneous nystagmus (SN), changes in postural control, and locomotor deviation
Because the decline in the frequency of SN after Unilateral labyrinthectomy (UL) indicates the development of the initial process of vestibular compensation (VC) in rats [7], our findings suggest that betahistine did not affect this process of VC after UL in these rats
We evaluated the effects of betahistine on the initial and late processes of VC in unilaterally labyrinthectomized rats (UL rats) by measuring the decrease in the frequency of SN and the decline in the number of MK801-induced Fos-positive neurons in the contra-MV, respectively

Summary

Introduction

Unilateral vestibular dysfunction causes spontaneous nystagmus (SN), changes in postural control, and locomotor deviation. The nystagmus and balance disorders recover gradually after the occurrence of the lesion. This functional restoration—based on the plasticity of the central vestibular system—is called vestibular compensation (VC) [1]. Unilateral labyrinthectomy (UL) causes a loss of resting activity in many neurons in the ipsilateral medial vestibular nucleus (ipsi-MVe), resulting in an imbalance in neural activity between the vestibular nuclei on each side of the brainstem. This imbalance in vestibular nuclear activities after UL induces SN. During the initial process of VC after UL, the suppression of the contralateral medial vestibular nucleus (contra-MVe) by the vestibular cerebellum–

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