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在6-羟基多巴胺损伤大鼠的基底神经节中,左旋千金藤啶碱和多巴胺激动剂诱导的旋转动作位点和单位放电

Action sites of rotation and unit firing induced by l-stepholidine and DA agonists in basal ganglia of 6-OHDA-lesioned rats.

作者信息

Zhang X X, Liu J, Fu Y, Hu G Y, Jin G Z

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Zhongguo Yao Li Xue Bao. 1999 Nov;20(11):979-86.

Abstract

AIM

To elucidate the action sites of l-stepholidine (SPD) in the basal ganglia.

METHODS

Counting the rotations after intra-nucleus microinjection and recording the neuron firing by microiontophoresis of SPD and DA agonists in the basal ganglia of 6-hydroxydopamine (6-OHDA)-lesioned rats.

RESULTS

The DA immunoreactive substance was markedly reduced in the 6-OHDA-lesioned rats. The intra-neostriatum microinjection of apomorphine (Apo, D1/D2), SK&F 38393 (D1), and SPD elicited remarkable rotation, and the characteristics of SK&F 38393-produced rotation were of long latency and long duration. The intra-substantia nigra pars reticulata (SNR) injection of Apo, SK&F 38393, and SPD induced the rotation response, while the selective D2 agonist quinpirole hydrochloride (Ly171555) did not because of scarce D2 receptors in the SNR. The intraglobus pallidus (GP) injection of DA agonists and SPD failed to evoke rotation, but the GP nucleus still had the contribution to rotation elicited by i.p. injection of DA agonists and SPD in the 6-OHDA-lesioned rats with successive kainic acid (KA) lesion. Besides, the successive lesion of entopeduncular nucleus (EP) on rotation was less important than that of GP nucleus. The microiontophoresis of Apo and SPD into the SNR could evoke the neuron firing, but failed to activate the GP neurons, which were activated by sodium glutamate (Glu) and inhibited by gamma-aminobutyric acid (GABA).

CONCLUSION

The action sites of SPD-induced rotation and neuron firing via the D1 receptors are in the neostriatum and SNR instead of GP. The direct neurocircuit through SNR is the most important for rotation of 6-OHDA-lesioned rats.

摘要

目的

阐明左旋千金藤啶碱(SPD)在基底神经节中的作用位点。

方法

对6-羟基多巴胺(6-OHDA)损伤大鼠的基底神经节进行核内微量注射后计数旋转次数,并通过微量离子电泳法记录SPD和多巴胺激动剂对神经元放电的影响。

结果

6-OHDA损伤大鼠中多巴胺免疫反应性物质明显减少。向新纹状体内微量注射阿扑吗啡(Apo,D1/D2)、SK&F 38393(D1)和SPD可引起明显的旋转,且SK&F 38393引起的旋转具有潜伏期长和持续时间长的特点。向黑质网状部(SNR)注射Apo、SK&F 38393和SPD可诱导旋转反应,而选择性D2激动剂盐酸喹吡罗(Ly171555)则不能,因为SNR中D2受体稀少。向苍白球(GP)注射多巴胺激动剂和SPD未能引起旋转,但在连续注射 kainic acid(KA)损伤的6-OHDA损伤大鼠中,GP核仍对腹腔注射多巴胺激动剂和SPD引起的旋转有贡献。此外,内囊核(EP)的连续损伤对旋转的影响不如GP核重要。将Apo和SPD微量离子电泳导入SNR可引起神经元放电,但未能激活GP神经元,而GP神经元可被谷氨酸(Glu)激活并被γ-氨基丁酸(GABA)抑制。

结论

SPD通过D1受体诱导旋转和神经元放电的作用位点在新纹状体和SNR而非GP。通过SNR的直接神经回路对6-OHDA损伤大鼠的旋转最为重要。

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