The role of GABAB receptors in the vestibular oculomotor system in mice.
The role of GABAB receptors in the vestibular oculomotor system in mice.
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DOI：
10.1016/j.bbr.2016.01.017
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发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Makishima T
中科院分区：
文献类型：
--
作者：
Shimizu N;Wood S;Kushiro K;Perachio A;Makishima T
全身施用 B 型γ-氨基丁酸 (GABAB) 受体激动剂巴氯芬会影响各种生理和心理过程。迄今为止，对灵长类动物动眼系统的影响已得到很好的表征，但对小鼠的影响尚未得到探索。在这项研究中，我们研究了巴氯芬对前庭相关眼球运动的影响。采用两种旋转范例，即正弦旋转和反向旋转来刺激内耳中的半规管和耳石器官。实验条件（剂量、途径和记录起始时间）是根据先前探索巴氯芬对小鼠行为影响的研究确定的。随着剂量的增加，耳管和耳石引起的眼部反应逐渐受到影响。药物敏感性存在明显的区别，表明源自直接前庭眼反射途径的眼球运动相对不变，而通过前庭系统中的高阶神经网络的反应则大幅下降。这些发现与在灵长类动物中观察到的结果一致，表明 GABAB 受体在额眼和侧眼动物的动眼神经系统中的作用非常保守。我们在这里展示了巴氯芬对小鼠前庭动眼功能的先前未被认识的影响。当解释药物作用下的一般动物表现时，应考虑平衡系统改变的潜在贡献。
Systemic administration of a gamma-amino butyric acid type B (GABAB) receptor agonist, baclofen, affects various physiological and psychological processes. To date, the effects on oculomotor system have been well characterized in primates, however those in mice have not been explored. In this study, we investigated the effects of baclofen focusing on vestibular-related eye movements. Two rotational paradigms, i.e. sinusoidal rotation and counter rotation were employed to stimulate semicircular canals and otolith organs in the inner ear. Experimental conditions (dosage, routes and onset of recording) were determined based on the prior studies exploring the behavioral effects of baclofen in mice. With an increase in dosage, both canal and otolith induced ocular responses were gradually affected. There was a clear distinction in the drug sensitivity showing that eye movements derived from direct vestibulo-ocular reflex pathways were relatively unaltered, while the responses through higher-order neural networks in the vestibular system were substantially decreased. These findings were consistent with those observed in primates suggesting a well-conserved role of GABAB receptors in the oculomotor system across frontal-eyed and lateral-eyed animals. We showed here a previously unrecognized effect of baclofen on the vestibular oculomotor function in mice. When interpreting general animal performance under the drug, the potential contribution of altered balance system should be taken into consideration.