Department of Pharmacology and Toxicology, School of Medical Sciences, and the Brain Health Research Centre, University of Otago Medical School, Dunedin, New Zealand.
Behav Brain Res. 2012 Feb 1;227(1):150-8. doi: 10.1016/j.bbr.2011.11.006. Epub 2011 Nov 15.
Rats and mice with bilateral vestibular loss exhibit dramatic locomotor hyperactivity and circling behaviours, which to date cannot be explained. Dysfunction of the striatal dopaminergic system is responsible for a number of known movement disorders and the D(2) dopamine receptor is known to be implicated. Therefore, it is possible that changes in striatal function are responsible for locomotor hyperactivity and circling following bilateral vestibular lesions. The aim of this study was to investigate the effects of the D(2) receptor antagonist, eticlopride (0.02, 0.04 and 0.06mg/kg; s.c.), on locomotor behaviour in rats at 5 months following bilateral vestibular deafferentation (BVD), using an open field maze. The levels of the D(2) receptor protein in the striatum were measured at 1 and 6 months post-BVD using western blotting. BVD rats exhibited locomotor hyperactivity and circling, which eticlopride did not eliminate. However, BVD rats did exhibit a decreased response to the inhibitory effect of eticlopride compared to sham controls at the 0.02 mg/kg dose. There were no changes in the amount of the D(2) receptor in the striatum at 1 or 6 months post-BVD; however, D(2) receptor levels were significantly higher on the right side than the left in both sham and BVD animals. These results suggest that locomotor hyperactivity and circling behaviours following BVD are not due simply to changes in D(2) receptor protein expression in the striatum and that other neurophysiological changes in the brain account for these behaviours following BVD.
双侧前庭损失的大鼠和小鼠表现出显著的运动过度活跃和转圈行为，迄今为止无法解释。纹状体多巴胺能系统的功能障碍是许多已知运动障碍的原因，并且已知 D2 多巴胺受体与之相关。因此，纹状体功能的变化可能是双侧前庭损伤后运动过度活跃和转圈的原因。本研究的目的是使用开放式场迷宫，在双侧前庭去传入（BVD）后 5 个月，研究 D2 受体拮抗剂（0.02、0.04 和 0.06mg/kg；皮下注射）对大鼠运动行为的影响。使用 Western blot 在 1 个月和 6 个月 BVD 后测量纹状体中 D2 受体蛋白的水平。BVD 大鼠表现出运动过度活跃和转圈，而 eticlopride 并不能消除这些行为。然而，与假手术对照组相比，BVD 大鼠在 0.02mg/kg 剂量下对 eticlopride 的抑制作用的反应性降低。BVD 后 1 或 6 个月，纹状体中 D2 受体的数量没有变化；然而，在假手术和 BVD 动物中，右侧的 D2 受体水平明显高于左侧。这些结果表明，BVD 后运动过度活跃和转圈行为不仅仅是由于纹状体中 D2 受体蛋白表达的变化引起的，而且大脑中的其他神经生理变化也导致了这些行为。
