Junya Fukuda1, Kazunori Matsuda2, Go Sato1, Tadashi Kitahara3, Momoyo Matsuoka1, Takahiro Azuma1, Yoshiaki Kitamura1, Koichi Tomita4, Noriaki Takeda1. 1. Department of Otolaryngology, Graduate School of Biomedical Sciences, University of Tokushima, Tokushima 770-8503, Japan. 2. Department of Otolaryngology, Tokushima Prefectural Central Hospital, Tokushima 770-8503, Japan. 3. Department of Otolaryngology Head and Neck Surgery, Nara Medical University, Kashihara 634-8522, Japan. 4. Department of Anatomy and Developmental Neurobiology, Institute of Biomedical Science, Graduate School, Tokushima University, Tokushima 770-8503, Japan.
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.
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.