INTERACTIONS OF CARBON MONOXIDE WITH PSYCHOACTIVE DRUGS

人类接触一氧化碳(CO)可能产生的不良后果是 环境健康科学中一个重要的关注领域。一 日益增长的科学兴趣问题令特殊人群感到担忧 接触一氧化碳的风险。人类经常会受到 处方药或自行给药的精神活性药物， 包括酒精、尼古丁、咖啡因、大麻和 各种镇静剂。神经毒性物质之间可能的相互作用 这些药物和一氧化碳(CO)的影响很大程度上 未经调查。我们将使用可操作的时间表控制行为 小鼠研究这些相互作用以确定未来可能的领域 深入研究动物和人类。已建立的方法和途径 由行为药理学家和毒物学家研究行为 将利用药物和毒物的影响。 我们提出了一种分层方法。目前，人们对此知之甚少 一氧化碳和药物的剧烈相互作用，因此似乎谨慎地 在进入长期低迷的可能后果之前，请考虑这些问题 浓缩性一氧化碳暴露。首先，我们将评估急性影响 CO单独作用和对老鼠行为的影响。从这项研究中，我们将选择三个 浓度，包括活性和非活性浓度，以供进一步研究 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、THC和 苯丙胺)。我们将在我们的条件下测定碳氧血红蛋白饱和度 相互作用中使用的CO浓度的暴露条件 学习。我们将为这九种药物分别建立剂量-效应曲线， 选择一种具有中等效应的剂量，并结合 三种浓度的CO以寻找增强或拮抗 效果。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 使用数学模型与一氧化碳的相互作用。这项研究也将有所帮助 确定低剂量的药物是否也会改变一氧化碳的影响。 展望了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.