Double K L, Crocker A D
Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1669-73. doi: 10.1073/pnas.92.5.1669.
The aim of the present study was to localize the dopamine receptors involved in the regulation of muscle tone. A strategy was used whereby the effects on muscle tone of injecting the irreversible dopamine receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in discrete brain regions were assessed. Increases in muscle tone were measured as changes in electromyographic activity of the gastrocnemius and tibialis muscles of conscious, unrestrained rats. No increases in muscle tone were found after injections of EEDQ into the anterior and posterior striatum, which produced marked reductions in dopamine receptor concentration. The effects of muscle tone of injecting EEDQ into the substantia nigra pars reticulata were also assessed. Large increases in muscle tone were observed associated with inactivation of either D1 or D2 dopamine receptors in the substantia nigra. The increased muscle tone was not reduced by subcutaneous administration of apomorphine, despite the presence of a normal population of striatal dopamine receptors. These findings provide evidence that dopamine receptors in the substantia nigra play an important role in the regulation of muscle tone. Further, they challenge the hypothesis that the muscle rigidity of Parkinson disease results primarily from loss of striatal dopamine receptor stimulation.
本研究的目的是定位参与调节肌张力的多巴胺受体。采用了一种策略，即评估在离散脑区注射不可逆多巴胺受体拮抗剂N-乙氧羰基-2-乙氧基-1,2-二氢喹啉（EEDQ）对肌张力的影响。肌张力的增加通过清醒、不受约束大鼠腓肠肌和胫骨前肌肌电图活动的变化来测量。将EEDQ注射到导致多巴胺受体浓度显著降低的前纹状体和后纹状体后，未发现肌张力增加。还评估了将EEDQ注射到黑质网状部对肌张力的影响。观察到黑质中D1或D2多巴胺受体失活会导致肌张力大幅增加。尽管纹状体多巴胺受体数量正常，但皮下注射阿扑吗啡并未降低增加的肌张力。这些发现提供了证据，表明黑质中的多巴胺受体在肌张力调节中起重要作用。此外，它们对帕金森病肌肉僵硬主要源于纹状体多巴胺受体刺激丧失这一假说提出了挑战。
