INTERACTIONS OF CARBON MONOXIDE WITH PSYCHOACTIVE DRUGS

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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.