BEHAVIORAL PHARMACOLOGY OF ABUSED AEROSOLS--CRACK

滥用气溶胶的行为药理学--裂纹

• 批准号: 2117417
• 负责人: RONALD W WOOD
• 金额: $ 48.16万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2117417
• 关键词: Macaca fascicularis; aerosols; behavior; bioassay; cardiovascular function; crack cocaine; dosage; drug metabolism; drug tolerance; gas chromatography; guinea pigs; inhalation drug abuse; inhalation drug administration; intravenous drug abuse; laboratory rat; light scattering; lung ischemia /hypoxia; mass spectrometry; methamphetamine; particle; pharmacokinetics; psychopharmacology; pulmonary respiration; reinforcer; respiratory airway volume; respiratory toxin; self stimulation; toxicant interaction; toxicology

Smoking is one of the predominant routes of administration of abused drugs such as heroin, phencyclidine, marihuana, tobacco and cocaine base ("crack"). Uptake is more rapid by inhalation than by the intranasal route, and the abuse potential of crack is at least as great as intravenously administered cocaine hydrochloride, if not greater, judging from clinical experience and the limited human literature. Unfortunately, there is a very limited animal literature on self-administration of cocaine base by inhalation, on its pharmacokinetics, or on repetitive use. We have developed technologies for generating aerosol atmospheres of cocaine which are repeatable and are appropriate for quinea pig and monkey. The refinement and of use of this exposure technology with these species will enable the characterization of cocaine self-administration and the pharmacology and toxicity unique to this route of self-administration. These techniques should facilitate subsequent laboratory investigations of cocaine and other drugs subject to abuse by this route, e.g., metham- phetamine hydrochloride. The goals for the next four years of this project include: 1) completing experiments on the aerosol physics of smoked drugs; 2) describing the abuse potential of cocaine base in self-administration sessions of limited duration in laboratory primates, with special attention to tolerance phenomena, and to concentration- and particle-size dependence of the behavior; 3) characterizing the effects of acute inhalation on conditioned behavior and on physiologic indices including: minute ventilation, pulmonary conductance (bronchodilation/constriction), arterial, pulmonary, and pulmonary wedge pressures, and heart rate in laboratory primates; 4) the description of acute and chronic toxicity syndromes, especially those expressed in pulmonary function and respiratory system structure. This will be done by characterizing the effects of acute inhalation on the cardiopulmonary function of guinea pigs: minute ventilation, pulmonary compliance, arterial pressures, heart rate, carbon monoxide diffusing capacity, and enzyme assays on pulmonary lavage fluids that are indicative of lung injury; 5) describing the pharmacokinetics of the agent following acute administration and brief (within--day) regimes of repeated administration. Arterial/venous differences will be described, as will the concentration-dependency of achieved levels by the inhalation and intravenous routes. 6) demonstration of the feasibility of applying these techniques to methamphetamine HCI smoking.

吸烟是滥用药物的主要途径之一 例如海洛因、苯环利定、大麻、烟草和可卡因 （“crack”）。 吸入比鼻内吸收更快。 路，和滥用潜力的裂纹是至少一样大， 静脉注射盐酸可卡因，如果不是更大，判断 临床经验和有限的人类文献。 不幸的是， 关于可卡因自我给药的动物文献非常有限 基于吸入、其药代动力学或重复使用。 我们有 开发了产生可卡因气溶胶的技术， 重复性好，适用于猪、猴。 的 改进和使用这种暴露技术与这些物种将 能够表征可卡因自我给药和 药理学和毒性独特的自我给药途径。 这些技术应有助于随后的实验室研究， 可卡因和通过这一途径滥用的其他药物，例如，甲硫氨酸， 盐酸非他明 该项目未来四年的目标是 包括以下步骤： 1)完成关于吸食毒品的气溶胶物理学的实验; 2)描述可卡因碱在自我给药中的滥用潜力 在实验室灵长类动物中进行有限时间的会话，特别注意 容忍现象，浓度和颗粒大小的依赖性 的行为; 3)描述急性吸入对条件行为的影响 和生理指标，包括：每分钟通气量、肺 传导（支气管扩张/收缩）、动脉、肺和 实验室灵长类动物的肺楔压和心率; 4)急性和慢性毒性综合征的描述，特别是 表现在肺功能和呼吸系统结构上。 这将通过表征急性吸入对 豚鼠的心肺功能：每分钟通气量，肺 顺应性、动脉压、心率、一氧化碳弥散 容量和肺灌洗液的酶测定， 肺损伤; 5)描述急性给药后药物的药代动力学 给药和重复给药的简短（日内）方案。 将描述动脉/静脉差异， 通过吸入达到的水平的浓度依赖性， 静脉途径。 6)证明将这些技术应用于 吸食冰毒