Department of Psychology, University of Michigan, Ann Arbor, MI48109-1043, USA.
Brain Res. 2010 Mar 31;1322:92-101. doi: 10.1016/j.brainres.2010.01.052. Epub 2010 Jan 28.
Studies of rodent grooming can provide valuable insight for dopamine contributions to the initiation, organization, and repetition of motor patterns. This information is useful for understanding how brain dysfunctions contribute to movement disorders such as Tourette syndrome and obsessive compulsive disorder, in which patients are driven to reiterate particular movement patterns. In rodents, dopamine D1 receptor stimulation causes a complex behavioral super-stereotypy in the form of excessive production and rigid execution of whole sequences of movements known as syntactic grooming chains. Sequential super-stereotypy of grooming chains may be particularly advantageous for modeling movement sequences and treatments in Tourette syndrome and related disorders. Here, we report that co-administration of haloperidol, one available treatment for Tourette syndrome and primarily a D2 receptor antagonist, prevented D1 stimulation with SKF38393 from inducing sequential super-stereotypy, which manifests as an exaggeration of the tendency to complete all four phases of a syntactic chain in rigid serial order once the first phase has begun. In a separate experiment, we showed that in contrast to acute D1 agonist administration, 39h withdrawal from chronic (3weeks) administration of the D1 antagonist SCH23390 (which has been suggested to increase D1 receptor expression in the basal ganglia) did not elicit sequential super-stereotypy after drug cessation. Instead, rats suddenly removed from repeated SCH23390 spent more time performing simple stereotypies that included intense scratching and biting behaviors. Together, these results have implications for understanding how dopamine receptors facilitate particular stereotypies manifest in animal models of Tourette syndrome and obsessive compulsive disorder.
对啮齿动物梳理行为的研究可以为多巴胺在运动模式的发起、组织和重复中的作用提供有价值的见解。这些信息有助于理解大脑功能障碍如何导致运动障碍,如妥瑞氏症和强迫症,患者会被迫重复特定的运动模式。在啮齿动物中,多巴胺 D1 受体刺激会导致复杂的行为超级刻板,表现为过度产生和严格执行称为句法梳理链的整个运动序列。梳理链的顺序超级刻板可能特别有利于建模妥瑞氏症和相关障碍中的运动序列和治疗。在这里,我们报告说,氟哌啶醇(一种用于妥瑞氏症的现有治疗方法,主要是 D2 受体拮抗剂)的共同给药可防止 D1 刺激与 SKF38393 一起诱导顺序超级刻板,这表现为一旦开始第一阶段,就会强烈倾向于以刚性顺序完成句法链的所有四个阶段。在另一个实验中,我们表明,与急性 D1 激动剂给药相反,在停止药物 39 小时后,从慢性(3 周)D1 拮抗剂 SCH23390(已被建议增加基底神经节中的 D1 受体表达)停药后,不会在停止药物后引发顺序超级刻板。相反,突然停止重复 SCH23390 的大鼠花费更多的时间进行简单的刻板行为,包括强烈的抓挠和咬行为。这些结果对于理解多巴胺受体如何促进妥瑞氏症和强迫症动物模型中特定刻板行为的表现具有重要意义。