BEHAVIORAL PHARMACOLOGY & TOXICOLOGY OF ABUSED INHALANTS

这项请求中提出的研究目的是 ADAMHA RSDA(II级)是为了推进行为 吸入剂的药理学和毒理学。科学含量 从NIDA正在进行的14年的拨款中增加了 刚刚被转移到纽约大学医疗中心的几年。 除了获得新的能力和 从我的新环境中独特的研究潜力中获利， 研究计划的具体目标保持不变： 吸入剂滥用模型的开发将提供技术 这：(1)允许评估以下物质的相对滥用潜力 溶剂和麻醉剂；(2)允许无毒规格 接触溶剂的水平和工业标准的建议 暴露限值；(3)允许比较 吸入剂维持的寻药行为 由其他滥用药物维持的行为。 拟议的计划将分阶段进行： 1)猴子的溶剂自我给药。集中度- 并将确定吸入剂的持续时间-效果曲线 作为烷基苯(如甲苯)、酮和脂肪醇。 将审查增援时间表，以确定 这些助剂作为增强剂的有效性。吸入性血药浓度 将会被确定。 2)吸入物质的厌恶特性。我们将生成 通过停止使用有毒吸入剂来维持业绩。 最初的厌恶可能在决定 滥用的可能性。使挥发性物质变得令人厌恶的技术 是最重要的，并可能直接影响到产品 配方。 3)有机溶剂对性能的影响。吸入材料 诱发行为毒性，可通过使用 计划控制的行为。浓度-效应曲线 将获得几种试剂来确定浓度如何 维持自我管理与那些影响 其他表演。这有助于确定它们的药理特性 个人资料和自我给药和药代动力学 数据，帮助我们了解吸入剂滥用的决定因素。

The purpose of the research proposed in this request for an ADAMHA RSDA (Level II) is to advance the behavioral pharmacology and toxicology of inhalants. The scientific content of the proposal grows from a NIDA grant in progress for fourteen years that has just been moved to the NYU Medical Center. Except for the opportunities to gain new competencies and to profit from the unique research potential of my new environment, the specific aims of the research program remains the same: The development of models of inhalant abuse will provide techniques that: (1) permit assessment of the relative abuse potential of solvents and anesthetics; (2) permit specification of nontoxic levels of solvent exposure and the recommendation of industrial exposure limit values; (3) permit comparison of the strength of inhalant-maintained drug-seeking behavior with the strength of behavior maintained by other drugs of abuse. The proposed program will proceed in parallel phases: 1) Solvent self-administration by the monkey. Concentration- and duration-effect curves will be determined for inhalants such as alkyl benzenes (e.g. toluene), ketones, and aliphatic alcohols. Schedules of reinforcement will be examined to determine the effectiveness of these agents as reinforcers. Inhalant blood levels will be determined. 2) Aversive properties of inhaled substances. We will generate performances maintained by the termination of noxious inhalants. Initial aversiveness may play an important role in determining abuse potential. Techniques to make volatile materials aversive are of paramount importance, and could bear directly on product formulation. 3) Effects of organic solvents on performance. Inhaled materials induce behavioral toxicity that can be measured by using schedule-controlled behavior. Concentration- effect curves of several agents will be obtained to determine how concentrations that maintain self-administration are related to those that affect other performances. This helps characterize their pharmacologic profiles and, with both self-administration and pharmacokinetic data, helps us understand the determinants of inhalant abuse.