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首页> 外文期刊>Alcohol >Ethanol and cocaine: Environmental place conditioning, stereotypy, and synergism in planarians
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Ethanol and cocaine: Environmental place conditioning, stereotypy, and synergism in planarians

机译：乙醇和可卡因：环境中的环境调节，刻板印象和协同作用

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More than 90% of individuals who use cocaine also report concurrent ethanol use, but only a few studies, all conducted with vertebrates, have investigated pharmacodynamic interactions between ethanol and cocaine. Planaria, a type of flatworm often considered to have the simplest 'brain,' is an invertebrate species especially amenable to the quantification of drug-induced behavioral responses and identification of conserved responses. Here, we investigated stereotypical and environmental place conditioning (EPC) effects of ethanol administered alone and in combination with cocaine. Planarians displayed concentration-related increases in C-shaped movements following exposure to ethanol (0.01-1%) (maximal effect: 9.9±1.1C-shapes/5min at 0.5%) or cocaine (0.1-5mM) (maximal effect: 42.8±4.1C-shapes/5min at 5mM). For combined administration, cocaine (0.1-5mM) was tested with submaximal ethanol concentrations (0.01, 0.1%); the observed effect for the combination was enhanced compared to its predicted effect, indicating synergism for the interaction. The synergy with ethanol was specific for cocaine, as related experiments revealed that combinations of ethanol and nicotine did not result in synergy. For EPC experiments, ethanol (0.0001-1%) concentration-dependently increased EPC, with significant environmental shifts detected at 0.01 and 1%. Cocaine (0.001-1μM) produced an inverted U-shaped concentration-effect curve, with a significant environmental shift observed at 0.01μM. For combined exposure, variable cocaine concentrations (0.001-1μM) were administered with a statistically ineffective concentration of ethanol (0.0001%). For each concentration of cocaine, the environmental shift was enhanced by ethanol, with significance detected at 1μM. Cocaethylene, a metabolite of cocaine and ethanol, also produced C-shapes and EPC. Lidocaine (0.001-10μM), an anesthetic and analog of cocaine, did not produce EPC or C-shaped movements. Evidence from planarians that ethanol produces place-conditioning effects and motor dysfunction, and interacts synergistically with cocaine, suggests that aspects of ethanol neuropharmacology are conserved across species.
机译：超过90％的使用可卡因的人还报告了同时使用乙醇，但是只有少数研究都是在脊椎动物中进行的，研究了乙醇和可卡因之间的药效相互作用。扁平虫是一种扁虫，通常被认为是最简单的“大脑”，它是一种无脊椎动物，特别适合对药物诱导的行为反应进行定量并确定保守反应。在这里，我们调查了单独和与可卡因联合使用的乙醇的定型和环境场所调节（EPC）效果。暴露于乙醇（0.01-1％）（最大作用：9.9±1.1C形/5min,0.5%）或可卡因（0.1-5mM）（最大作用：42.8±在5mM时4.1C形状/ 5min）。对于联合给药，可卡因（0.1-5mM）的乙醇浓度低于最大浓度（0.01，0.1％）。与预期效果相比，该组合的观察效果有所增强，表明了相互作用的协同作用。与乙醇的协同作用对可卡因具有特异性，因为相关实验表明，乙醇和尼古丁的组合不会产生协同作用。对于EPC实验，乙醇（0.0001-1％）浓度依赖性地增加了EPC，在0.01和1％处检测到明显的环境变化。可卡因（0.001-1μM）产生一条倒U形的浓度效应曲线，在0.01μM处观察到明显的环境变化。对于联合暴露，给予可卡因浓度可变（0.001-1μM）和统计学上无效的乙醇浓度（0.0001％）。对于每种浓度的可卡因，乙醇都可提高环境变化，在1μM时检测到显着性。可卡因，可卡因和乙醇的代谢产物，也产生C形和EPC。麻醉剂和可卡因类似物利多卡因（0.001-10μM）不会产生EPC或C形运动。涡虫学家的证据表明，乙醇会产生位置调节作用和运动功能障碍，并与可卡因协同作用，这表明跨物种保护了乙醇神经药理学的各个方面。

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