Department of Functional Biology and Health Sciences, University of Vigo, Spain.
Toxicology. 2012 Dec 16;302(2-3):197-202. doi: 10.1016/j.tox.2012.07.017. Epub 2012 Aug 9.
Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter.
氯噻啉（CLO）是一种具有烟碱型乙酰胆碱受体选择性作用的新烟碱类杀虫剂。本研究旨在使用自由活动和清醒大鼠的微透析技术，确定 CLO 诱导纹状体多巴胺释放的神经化学基础。纹状体内给予 CLO（3.5mM）可增加自发（相对于基础值增加 2462±627%）和 KCl 诱发的（相对于基础值增加 4672±706%）多巴胺释放。在无钙介质中，该作用减弱，在利血平预处理的动物或存在河豚毒素（TTX）的情况下被阻止。为了研究多巴胺转运体（DAT）的参与，观察了 CLO 在可乐定存在下的作用。CLO 和可乐定的共同给药对纹状体多巴胺释放产生相加作用。结果表明，CLO 对纹状体多巴胺释放的作用主要是通过胞吐机制、Ca2+、囊泡和 TTX 依赖性机制介导的，而不是通过多巴胺转运体介导的机制。
