LICIT AND ILLICIT ABUSED DRUGS--BEHAVIORAL INTERACTIONS

申请人摘要： 一系列的研究提出了在正常人受试者和受试者 有吸毒史的人来调查几个主要的行为 咖啡因与经典药物的药理作用 滥用：身体依赖性/耐受性，歧视性刺激效应， 和强化效果。 研究将在非- 住宅和住宅实验室研究设置。 药物将 以胶囊或静脉注射的方式给药， 设盲条件和给药或终止的影响 将使用主观、行为和/或 生理措施。 一系列的三项研究将扩大 研究人员对咖啡因身体依赖性的研究。 前三 将提供药理学特异性信息， 通过使用药物辨别的变化的作用机制 程序比较咖啡因与茶碱，d-安非他明和 三氮唑。 其中一项研究将调查 对咖啡因和这些其他物质的区别作用的敏感性 化合物. 另外两项研究将描述 在接受过辨别训练的受试者中， 低剂量咖啡因与安慰剂或低剂量d-安非他明与安慰剂。两个 其他研究将使用歧视程序作为基线， 表征咖啡因耐受性并试图提高咖啡因 加固. 最后的歧视研究将涉及应用 研究人员的低剂量咖啡因辨别程序， 在受试者中开发低剂量口服可卡因辨别模型， 吸毒史 最后一组三项研究将描述 主观、心理表现、生理和强化 静脉注射咖啡因的效果。 两项受试者研究 有药物滥用史的人将研究咖啡因的作用 剂量和静脉注射持续时间，并将比较咖啡因与 其他精神刺激药物可卡因，d-安非他明和 尼古丁。 最终研究将使用相同的程序来比较 正常人静脉注射咖啡因和尼古丁。 这项关于咖啡因和其他经典精神兴奋剂的研究 应该可以促进对行为药理学机制的理解 潜在的药物滥用/依赖。 鉴于广泛合法使用 咖啡因，该项目也将具有临床重要性， 确定易受咖啡因身体依赖影响的决定因素 和强化作用，以及发展咖啡因- 使用减少或停止计划以及计划， 咖啡因相关的健康风险。

APPLICANT'S ABSTRACT: A series of studies is proposed in normal human subjects and in subjects with histories of drug abuse to investigate several major behavioral- pharmacological effects that caffeine shares with classic drugs of abuse: physical dependence/tolerance, discriminative stimulus effects, and reinforcing effects. Studies will be conducted in both non- residential and residential laboratory research settings. Drugs will be administered in capsules or by intravenous injection under double- blind conditions and the effects of drug administration or termination of chronic dosing will be assessed using subjective, behavioral and/or physiological measures. A series of three studies will extend the investigators' work on caffeine physical dependence. The first three of these will provide information about pharmacological specificity and mechanisms of action by using variations on drug discrimination procedures to compare caffeine with theophylline, d-amphetamine and triazloam. One study will investigate individual differences in sensitivity to the discriminative effects of caffeine and these other compounds. Two other studies will characterize the profiles of generalization in subjects trained on discriminations involving either low-dose caffeine vs. placebo or low-dose d-amphetamine vs. placebo.Two other studies will use discrimination procedures as a baseline for characterizing caffeine tolerance and for attempting to enhance caffeine reinforcement. The final discrimination study will involve application of the investigators' low-dose caffeine discrimination procedures to develop a low-dose oral cocaine discrimination model in subjects with histories of drug abuse. A final set of three studies will characterize subjective, psychomotor performance, physiological and reinforcing effects of intravenously administered caffeine. Two studies in subjects with histories of drug abuse will investigate the effects of caffeine dose and intravenous injection duration, and will compare caffeine with the other psychomotor stimulant drugs cocaine, d-amphetamine and nicotine. A final study will use identical procedures to compare the intravenous administration of caffeine and nicotine in normal subjects. This research with caffeine and other classic psychomotor stimulants should advance understanding of behavioral-pharmacological mechanisms underlying drug abuse/dependence. Given the widespread licit use of caffeine, this project will also be of clinical importance in identifying determinants of vulnerability to caffeine physical dependence and reinforcement in the general population and to developing caffeine- use reduction or cessation programs as well as programs for minimizing caffeine-associated health risks.