INTERACTIONS OF CARBON MONOXIDE WITH PSYCHOACTIVE DRUGS

人类暴露于一氧化碳（CO）可能产生的不良后果是 这是环境健康科学的一个重要领域。 一 一个日益引起科学兴趣的问题涉及特殊人群， 一氧化碳暴露风险。 人类经常受到 处方或自行服用的精神药物， 包括常见的酒精、尼古丁、咖啡因、大麻， 各种镇静剂 神经毒性物质与 这些药物和一氧化碳（CO）的作用主要是 未经调查 我们将使用操作性的时间表控制的行为， 小鼠研究这些相互作用，以确定未来可能的领域 在动物和人类身上进行深入研究。 确定的方法和方针 由行为药理学家和毒理学家来研究 将利用药物和毒物的作用。 我们提出了一个分层的方法。 目前，人们对它知之甚少。 CO和药物的急性相互作用，因此， 在讨论长期低利率可能造成的后果之前， 高浓度CO暴露。 首先，我们将评估急性影响 和小鼠行为的影响。 从这个研究中，我们将选择三个 浓度，包括活性和非活性浓度，供进一步研究 与九种典型的精神活性药物（乙醇，尼古丁， 咖啡因，安定，氯丙嗪，戊巴比妥，吗啡，四氢大麻酚和 安非他明）。 我们将根据我们的 相互作用中使用的CO浓度的暴露条件 问题研究 我们将为九种药物中的每一种建立剂量效应曲线， 选择一种具有中等效果的剂量，并结合以下药物进行测试： 三种浓度的CO，以寻找增强或拮抗 方面的影响. 在这项初步研究中，我们将选择两种药物， 可能的相互作用，并更全面地表征和量化 使用数学模型与CO相互作用。 这项研究也将有助于 确定低剂量的药物是否也会改变CO的作用。 该项目的未来发展方向。

Possible adverse consequences of human exposure to carbon monoxide (CO) is an important area of concern in the environmental health sciences. One question of increasing scientific interest concerns special populations at risk for CO exposure. Humans very often are under the influence of psychoactive drugs which are prescribed or which they self-administer, including such common ones as alcohol, nicotine, caffeine, marihuana, and various tranquilizers. Possible interactions between the neurotoxic effects of these drugs and carbon monoxide (CO) are largely uninvestigated. We will use the operant schedule-controlled behavior of mice to study these interactions to ascertain possible areas for future in-depth study in animals and humans. Methods and approaches established by behavioral pharmacologists and toxicologists to study the behavioral effects of drugs and toxicants will be utilized. We propose a tiered approach. At the present time very little is known of acute interactions of CO and drugs, consequently it seems prudent to consider these before moving to possible consequences of prolonged lower concentration CO exposures. Initially we will evaluate the acute effects of CO alone and on mouse behavior. From this study we will choose three concentrations, including both active and inactive ones, for further study in combination with nine typical psychoactive drugs (ethanol, nicotine, caffeine, diazepam, chlorpromazine, pentobarbital, morphine, THC and amphetamine). We will determine the carboxyhemoglobin saturation under our exposure conditions for the concentrations of CO used in the interaction studies. We will establish dose-effect curves for each of the nine drugs, choose a dose with intermediate effects, and test it in combination with the three concentrations of CO to look for enhancement or antagonism of effects. For this initial study we will choose two drugs with the greatest possible interactions, and more completely characterize and quantitate the interaction with CO using a mathematical model. This study will also help establish whether the drugs at low doses also modify the effects of CO. Future directions for this project are presented.