Locomotor activating effects of cocaine and scopolamine combinations in rats: isobolographic analysis.
Locomotor activating effects of cocaine and scopolamine combinations in rats: isobolographic analysis.
复制标题
可卡因和东莨菪碱组合对大鼠的运动激活作用：等辐射分析。
DOI：
10.1097/fbp.0000000000000043
复制
发表时间：
2014
影响因子：
1.6
通讯作者：
Thomsen,Morgane
中科院分区：
文献类型：
--
作者：
Thomsen,Morgane
毒蕈碱胆碱能受体目前作为治疗各种精神疾病的可行靶点而重新受到关注。多巴胺能和毒蕈碱系统以复杂的方式相互作用。本研究的目的是在行为水平上量化系统给予的精神兴奋剂和毒蕈碱拮抗剂之间的相互作用。通过对自发活动数据的等效线分析，我们评估了三种可卡因/东莨菪碱混合物在四个效应水平下偏离简单剂量添加（加和性）的影响。所有三种混合物都产生了一些超过加和（协同）效应，因为相对于加和剂量的计算效应，产生给定效应所需的剂量较低。可卡因和东莨菪碱具有可比贡献的混合物产生了显着超过加性效应，但在所有最低的效果水平检查。主要是可卡因的混合物是超过加性只有在低的效果水平，而主要是东莨菪碱的混合物产生的效果更符合加性，只有最高的效果水平几乎没有达到显着的协同作用。我们的研究证实并量化了先前的研究结果，表明兴奋剂和毒蕈碱拮抗剂的协同作用。协同作用意味着可卡因和东莨菪碱通过不同的途径刺激自发活动，并且对于含有可比比例的可卡因和东莨菪碱的混合物最明显。
Muscarinic cholinergic receptors are currently receiving renewed interest as viable targets for treating various psychiatric disorders. Dopaminergic and muscarinic systems interact in complex ways. The goal of this study was to quantify the interaction between a systemically administered psychomotor stimulant and muscarinic antagonist at the behavioral level. Through isobolographic analysis of locomotor activity data, we assessed the effects of three cocaine/scopolamine mixtures in terms of deviation from simple dose addition (additivity), at four effect levels. All three mixtures produced some more-than-additive (synergistic) effects, as lower doses were needed to produce the given effects relative to the calculated effect of additive doses. A mixture with comparable contributions from cocaine and scopolamine produced significantly more-than-additive effects at all but the lowest effect level examined. A mostly-cocaine mixture was more-than-additive only at low effect levels, whereas a mostly-scopolamine mixture produced effects more consistent with additivity, with only the highest effect level barely reaching significant synergism. Our study confirms and quantifies previous findings that suggested synergistic effects of stimulants and muscarinic antagonists. The synergism implies that cocaine and scopolamine stimulate locomotor activity through nonidentical pathways, and was most pronounced for a mixture containing cocaine and scopolamine in comparable proportions.