Fernando J C, Hoskins B, Ho I K
Life Sci. 1986 Dec 8;39(23):2169-76. doi: 10.1016/0024-3205(86)90393-0.
The role of brain dopamine (DA) in the enhancement of muscarinic antagonist-induced hyperactivity was investigated. The effects of atropine and scopolamine on the concentrations of DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), following DFP administration were determined. In control animals, atropine and scopolamine decreased the concentration of DA and increased the ratios of DOPAC/DA and HVA/DA in the striatum, but not in the N. accumbens - T. olfactorium (mesolimbic) area. Following a single dose of DFP, the two antimuscarinic drugs caused decreases of DA and further increases of the above ratios in both brain regions. However, following repeated DFP treatment for 2 weeks, these antimuscarinic drug-induced changes were observed only in the mesolimbic area, but not in the striatum. It is suggested that an increased DA turnover, indicated by elevated DOPAC/DA and HVA/DA ratios, underlies the muscarinic antagonist-induced hyperactivity. The well-known occurrence of muscarinic receptor down-regulation after DFP administration, could be responsible for the enhancement of the actions of muscarinic antagonists in DFP-treated animals. The observed differential effect on DA turnover in the two broad areas may involve both muscarinic and DA receptors.
研究了脑多巴胺（DA）在毒蕈碱拮抗剂诱导的多动增强中的作用。测定了给予二异丙基氟磷酸酯（DFP）后，阿托品和东莨菪碱对DA及其代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）浓度的影响。在对照动物中，阿托品和东莨菪碱降低了纹状体中DA的浓度，并增加了DOPAC/DA和HVA/DA的比值，但在伏隔核-嗅结节（中脑边缘）区域未出现这种情况。给予单剂量DFP后，这两种抗毒蕈碱药物在两个脑区均导致DA减少以及上述比值进一步升高。然而，在DFP重复治疗2周后，这些抗毒蕈碱药物诱导的变化仅在中脑边缘区域观察到，而在纹状体中未观察到。提示DOPAC/DA和HVA/DA比值升高所表明的DA周转增加是毒蕈碱拮抗剂诱导多动的基础。DFP给药后众所周知的毒蕈碱受体下调现象，可能是DFP处理动物中毒蕈碱拮抗剂作用增强的原因。在这两个广泛区域观察到的对DA周转的不同影响可能涉及毒蕈碱受体和DA受体。
