The effects of continuous administration of diazepam on the recovery of lesion-induced nystagmus in unilaterally labyrinthectomised rats

Abstract

Background

Diazepam, a gamma-aminobutyric acid type A receptor agonist, is classified as a vestibular suppressant and is effective in treating acute vertigo. However, its effects on vestibular compensation (VC) remain unclear.

Objectives

We examined the effects of continuous administration of diazepam on the frequency of spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) as an index of the initial process of VC in rats.

Materials and methods

Diazepam was continuously administered at doses of 3.5 and 7.0 mg/kg/day, intraperitoneally, via an osmotic minipump. The frequency of SN beating against the lesion side after UL was measured. Potassium chloride (KCl) solution (1 M) was injected intratympanically to induce SN beating to the injection side.

Results

Continuous administration of diazepam significantly and dose-dependently decreased the frequency of SN after UL, and also reduced the x intercept of the nonlinear regression curve of the decline in UL-induced SN with time in rats. However, the continuous administration of diazepam did not affect the frequency of intratympanic KCl-induced SN in the rats.

Conclusion

These findings suggested that continuous administration of diazepam accelerates the initial process of VC; however, it does not suppress the nystagmus-driving mechanisms in rats.

Chinese Abstract

背景：地西泮是一种γ-氨基丁酸型受体激动剂, 被归类为前庭抑制剂, 可有效治疗急性眩晕。 然而, 它对前庭代偿（Vc）的作用尚不明确。

目的：我们研究了连续地西泮给药对单侧迷路切除术（Ul）后自发性眼球震颤（sN）频率的影响, 这种频率可用作大鼠 前庭代偿 初始过程的指标。

材料和方法：通过微型渗透泵经腹膜内连续施用地西泮, 剂量为 3.5 和 7.0mg/公斤/天。 测量 Ul 后 sN 敲击病变侧的频率。 鼓室内注射氯化钾 (Kcl) 溶液 (1M), 以诱导 sN 向注射侧跳动。

结果：连续给药地西泮可显著且呈剂量依赖性地降低Ul后大鼠的sN频率, 并且降低了Ul诱导的大鼠sN随时间下降的非线性回归曲线的x截距。 然而, 连续给药地西泮并不影响大鼠鼓室内Kcl诱导的sN频率。

结论：这些研究结果表明, 持续施用地西泮可加速前庭代偿的初始过程； 然而, 它不会抑制大鼠的眼球震颤驱动机制。

Keywords:

• Vestibular compensation
• diazepam
• GABA
• spontaneous nystagmus
• unilateral labyrinthectomy
• rats

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by JSPS KAKENHI Grant Number JP19K09911.