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向豚鼠前庭神经核复合体慢性输注γ-氨基丁酸A型(GABAA)受体激动剂或拮抗剂对前庭代偿的影响。

Effects of chronic infusion of a GABAA receptor agonist or antagonist into the vestibular nuclear complex on vestibular compensation in the guinea pig.

作者信息

Gliddon Catherine M, Darlington Cynthia L, Smith Paul F

机构信息

Vestibular Research Group, Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand.

出版信息

J Pharmacol Exp Ther. 2005 Jun;313(3):1126-35. doi: 10.1124/jpet.104.082172. Epub 2005 Feb 1.

Abstract

The aim of this study was to determine the effects of chronic infusion of a GABA(A) receptor agonist/antagonist into the ipsilateral or contralateral vestibular nuclear complex (VNC) on vestibular compensation, the process of behavioral recovery that occurs after unilateral vestibular deafferentation (UVD). This was achieved by a mini-osmotic pump that infused, over 30 h, muscimol or gabazine into the ipsilateral or contralateral VNC. Spontaneous nystagmus (SN), yaw head tilt (YHT), and roll head tilt (RHT) were measured. Infusion of muscimol or gabazine into either the ipsilateral or the contralateral VNC had little effect on SN compensation. In contrast, infusion of muscimol (250, 500, and 750 ng) into the contralateral VNC and gabazine (31.25, 62.5, and 125 ng) into the ipsilateral VNC significantly affected YHT and RHT (p < 0.05), but not their rate of compensation (p > 0.05). Interestingly, the effects of muscimol and gabazine on YHT and RHT were consistent throughout the first 30 h post-UVD. Infusion of muscimol (62.5, 125, and 250 ng) into the ipsilateral VNC and gabazine (125, 375, and 750 ng) into the contralateral VNC had little effect on YHT and RHT or their rate of compensation. These results suggest that the ipsilateral gabazine and contralateral muscimol infusions are modifying the expression of the symptoms without altering the mechanism of compensation. Furthermore, the neurochemical mechanism responsible for vestibular compensation can cope with the both the GABA(A) receptor-mediated and the UVD-induced decrease in resting activity.

摘要

本研究的目的是确定向同侧或对侧前庭神经核复合体(VNC)慢性输注GABA(A)受体激动剂/拮抗剂对前庭代偿的影响,前庭代偿是单侧前庭去传入(UVD)后发生的行为恢复过程。这是通过一个微型渗透泵实现的,该泵在30小时内将蝇蕈醇或荷包牡丹碱注入同侧或对侧VNC。测量了自发性眼球震颤(SN)、偏航性头部倾斜(YHT)和侧滚性头部倾斜(RHT)。向同侧或对侧VNC注入蝇蕈醇或荷包牡丹碱对SN代偿影响不大。相比之下,向对侧VNC注入蝇蕈醇(250、500和750 ng)以及向同侧VNC注入荷包牡丹碱(31.25、62.5和125 ng)对YHT和RHT有显著影响(p < 0.05),但对它们的代偿速率没有影响(p > 0.05)。有趣的是,蝇蕈醇和荷包牡丹碱对YHT和RHT的影响在UVD后的前30小时内是一致的。向同侧VNC注入蝇蕈醇(62.5、125和250 ng)以及向对侧VNC注入荷包牡丹碱(125、375和750 ng)对YHT和RHT或其代偿速率影响不大。这些结果表明,同侧注入荷包牡丹碱和对侧注入蝇蕈醇正在改变症状的表现,而不改变代偿机制。此外,负责前庭代偿的神经化学机制能够应对GABA(A)受体介导的和UVD诱导的静息活动降低。

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