Matsumoto R R, Aziz N, Truong D D
University of California Irvine, Department of Neurology, Parkinson and Movement Disorders Program 92717, USA.
Pharmacol Biochem Behav. 1995 Apr;50(4):533-8. doi: 10.1016/0091-3057(94)00336-x.
We have previously reported the presence of posthypoxic, audiogenic myoclonus in rats after cardiac arrest and the ability of the 5-HT precursor, 5-HTP, to attenuate these muscle jerks. In addition, we have recently shown that 5-HT2 and 5-HT3 agonists can reduce the severity of myoclonus in these animals, suggesting a deficiency in serotonergic neurotransmission. In the present study, the levels of 5-HTP, 5-HT, and 5-HIAA were measured in seven regions of the brain in myoclonic and normal rats to identify the areas of the brain in which a serotonergic dysfunction resides. Similar to previous studies, we observed pronounced posthypoxic, audiogenic myoclonus 3 and 14 days after resuscitation from cardiac arrest, with a resolution of the abnormal movements by 45 days postarrest. HPLC measurements revealed significant changes in indole levels in the following areas of the brain: cortical 5-HIAA, striatal 5-HT, striatal 5-HIAA, hippocampal 5-HT, mesencephalic 5-HIAA, myelencephalic 5-HT, myelencephalic 5-HIAA, cerebellar 5-HTP, and cerebellar 5-HT. The changes in striatal 5-HT, cortical 5-HIAA, and mesencephalic 5-HIAA appear most relevant to the pathophysiology of posthypoxic myoclonus because regression analyses showed significant correlations between the myoclonus scores of the animals and the levels of these indoles. Based on the observed pattern of results, we postulate a dysfunction in serotonergic lateral (cortical) and far lateral (extrapyramidal) ascending pathways in posthypoxic myoclonus.
我们之前曾报道过，大鼠心脏骤停后会出现缺氧后听源性肌阵挛，以及5-羟色胺前体5-羟色氨酸（5-HTP）减轻这些肌肉抽搐的能力。此外，我们最近还表明，5-HT2和5-HT3激动剂可减轻这些动物的肌阵挛严重程度，提示血清素能神经传递存在缺陷。在本研究中，我们测量了肌阵挛大鼠和正常大鼠大脑七个区域中5-HTP、5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）的水平，以确定存在血清素能功能障碍的脑区。与之前的研究相似，我们观察到心脏骤停复苏后3天和14天出现明显的缺氧后听源性肌阵挛，骤停后45天异常运动消失。高效液相色谱测量显示，大脑以下区域的吲哚水平有显著变化：皮质5-HIAA、纹状体5-HT、纹状体5-HIAA、海马体5-HT、中脑5-HIAA、延髓5-HT、延髓5-HIAA、小脑5-HTP和小脑5-HT。纹状体5-HT、皮质5-HIAA和中脑5-HIAA的变化似乎与缺氧后肌阵挛的病理生理学最为相关，因为回归分析显示，动物的肌阵挛评分与这些吲哚的水平之间存在显著相关性。根据观察到的结果模式，我们推测缺氧后肌阵挛中血清素能外侧（皮质）和远外侧（锥体外系）上行通路存在功能障碍。
