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对大鼠单侧给予溴氰菊酯后,其转圈行为与纹状体多巴胺活性之间的分离。

Dissociation between circling behaviour and striatal dopamine activity following unilateral deltamethrin administration to rats.

作者信息

Brodie M E, Opacka J

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1985 Dec;331(4):341-6. doi: 10.1007/BF00500816.

Abstract

The neurotoxic pyrethroid, deltamethrin, induces a severe motor syndrome characterised by tremor and choreoathetosis when injected systemically to rats. The interaction between deltamethrin and the two major dopaminergic pathways - the nigrostriatal and mesolimbic pathways - was investigated in rats. Striatal catecholamines, indoleamines and metabolites were measured by HPLC with electrochemical detection. Unilateral injection of deltamethrin (1.0 microgram) into the ventral tegmental nucleus or substantia nigra induced rapid ipsilateral or contralateral circling respectively but was ineffective at other basal ganglia sites. Both the sham and vehicle injections at either site, resulted in a marked increase above normal in DA turnover in the ipsilateral striatum without inducing circling behaviour. DA turnover was increased to the same extent in the ipsilateral stratum of deltamethrin-treated rats where rapid circling was present. Therefore the neurochemical findings were not consistent with the rotation theories based on striatal DA asymmetry but rather followed alternative mechanisms previously proposed, where circling behaviour can occur by mechanisms not causally related to striatal DA. These findings also indicate that a degree of selectivity exists in the action of deltamethrin, a sodium channel toxin that might be expected to act on all neuronal systems within the SN or VTN or equally at other sites within the basal ganglia associated with circling behaviour.

摘要

神经毒性拟除虫菊酯溴氰菊酯经全身注射给大鼠后,会引发一种以震颤和舞蹈手足徐动症为特征的严重运动综合征。研究了大鼠体内溴氰菊酯与两条主要多巴胺能通路——黑质纹状体通路和中脑边缘通路——之间的相互作用。采用高效液相色谱电化学检测法测定纹状体中的儿茶酚胺、吲哚胺及其代谢产物。向腹侧被盖核或黑质单侧注射溴氰菊酯(1.0微克)分别诱导快速的同侧或对侧转圈行为,但在其他基底神经节部位无效。在任一部位进行假注射和溶剂注射,均导致同侧纹状体中多巴胺周转率显著高于正常水平,且未诱导转圈行为。在出现快速转圈行为的溴氰菊酯处理大鼠的同侧纹状体中,多巴胺周转率升高到相同程度。因此,神经化学研究结果与基于纹状体多巴胺不对称性的旋转理论不一致,而是遵循先前提出的其他机制,即转圈行为可通过与纹状体多巴胺无因果关系的机制发生。这些发现还表明,溴氰菊酯(一种钠通道毒素,可能预期作用于黑质或腹侧被盖核内的所有神经元系统,或同样作用于与转圈行为相关的基底神经节内的其他部位)的作用存在一定程度的选择性。

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