BEHAVIORAL PHARMACOLOGY OF ABUSED AEROSOLS - 'CRACK'

滥用气溶胶的行为药理学 - “裂纹”

• 批准号: 3211097
• 负责人: RONALD W WOOD
• 金额: $ 35.6万
• 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/3211097
• 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。 如海洛因、苯环利定、大麻、烟草和可卡因 (“快克”)。吸入比鼻腔吸收更快。 路径，而破解的滥用潜力至少与 静脉注射盐酸可卡因，如果不是更大的话，判断 来自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。 以吸入、药代动力学或重复使用为基础。我们有 开发了产生可卡因气溶胶大气的技术， 是可重复的，适用于豚鼠和猴子。这个 在这些物种中改进和使用这种暴露技术将 使可卡因自我给药的特征和 这种自我给药途径所特有的药理和毒性。 这些技术应该有助于随后的实验室调查 可卡因和其他可通过这种途径滥用的药物，例如冰毒- 盐酸非他明。该项目未来四年的目标 包括： 1)完成吸食毒品的气溶胶物理实验； 2)描述可卡因碱在自我管理中的滥用潜力 实验室灵长类动物的有限持续时间会话，并给予特别关注 对耐受现象以及对浓度和颗粒大小的依赖 对行为的影响； 3)描述急性吸入对条件性行为的影响 生理指标包括：分钟通气量、肺活量 电导(支气管扩张/收缩)、动脉、肺和 实验灵长类动物的肺楔压和心率； 4)急性和慢性中毒症状的描述，特别是 在肺功能和呼吸系统结构中表达。 这将通过表征急性吸入对人体的影响来实现。 豚鼠的心肺功能：分钟通气量、肺活量 顺应性、动脉压、心率、一氧化碳弥散 肺灌洗液的容量和酶分析具有指示性 肺损伤； 5)描述药物在急性发作后的药代动力学 行政和简短的(在一天内)重复行政的制度。 将描述动脉/静脉的差异，以及 吸入和吸入所达到水平的浓度依赖关系 静脉注射。 6)演示将这些技术应用于 吸食盐酸甲基苯丙胺。