Key role of striatal cholinergic interneurons in processes leading to arrest of motor stereotypies
Key role of striatal cholinergic interneurons in processes leading to arrest of motor stereotypies
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DOI：
10.1093/brain/awq285
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发表时间：
2011-01-01
期刊：
影响因子：
14.5
通讯作者：
Kemel, Marie-Louise
中科院分区：
文献类型：
--
作者：
Aliane, Verena;Perez, Sylvie;Kemel, Marie-Louise
运动刻板是各种疾病的关键症状，如图雷特综合征和punding。尼古丁或胆碱酯酶抑制剂的管理是有效的，在治疗这些症状。然而，胆碱能传递在运动刻板症中的作用仍然未知。在强烈的可卡因诱导的运动刻板印象，我们表明，增加多巴胺释放的结果减少在背侧纹状体的领土相关的前额叶皮层的乙酰胆碱释放。在这里，我们调查的作用，纹状体胆碱能传输的逮捕运动刻板。分析N-甲基-D-天冬氨酸诱发释放的多巴胺和乙酰胆碱在强度下降的运动刻板反应揭示了多巴胺和乙酰胆碱释放之间的分离。而多巴胺的释放仍然增加，抑制乙酰胆碱释放减少，反映了运动刻板的时间过程。此外，恢复纹状体乙酰胆碱释放的药物治疗（雷氯必利，多巴胺D2拮抗剂;背侧纹状体前额叶区域的腹膜内或局部注射）迅速停止了运动刻板症。相反，药物治疗，阻断乙酰胆碱（东莨菪碱，毒蕈碱拮抗剂;腹腔内或纹状体局部注射）或诱导变性的胆碱能中间神经元（AF 64 A，胆碱能毒素）在背侧纹状体的前额区的突触后效应，强劲的延长了持续时间的强运动刻板。因此，我们提出，恢复胆碱能传输在背侧纹状体的前额领土起着关键作用，在逮捕的电机刻板。
Motor stereotypy is a key symptom of various disorders such as Tourette's syndrome and punding. Administration of nicotine or cholinesterase inhibitors is effective in treating some of these symptoms. However, the role of cholinergic transmission in motor stereotypy remains unknown. During strong cocaine-induced motor stereotypy, we showed earlier that increased dopamine release results in decreased acetylcholine release in the territory of the dorsal striatum related to the prefrontal cortex. Here, we investigated the role of striatal cholinergic transmission in the arrest of motor stereotypy. Analysis of N-methyl-d-aspartic acid-evoked release of dopamine and acetylcholine during declining intensity of motor stereotypy revealed a dissociation between dopamine and acetylcholine release. Whereas dopamine release remained increased, the inhibition of acetylcholine release decreased, mirroring the time course of motor stereotypy. Furthermore, pharmacological treatments restoring striatal acetylcholine release (raclopride, dopamine D2 antagonist; intraperitoneal or local injection in prefrontal territory of the dorsal striatum) rapidly stopped motor stereotypy. In contrast, pharmacological treatments that blocked the post-synaptic effects of acetylcholine (scopolamine, muscarinic antagonist; intraperitoneal or striatal local injection) or induced degeneration of cholinergic interneurons (AF64A, cholinergic toxin) in the prefrontal territory of the dorsal striatum robustly prolonged the duration of strong motor stereotypy. Thus, we propose that restoration of cholinergic transmission in the prefrontal territory of the dorsal striatum plays a key role in the arrest of motor stereotypy.