BEHAVIORAL PHARMACOLOGY & TOXICOLOGY OF ABUSED INHALANTS

本申请中提出的研究目的是为了 ADAMHA RSDA（二级）是为了提高行为 吸入剂的药理学和毒理学。 科学内涵 该提案的增长从一个NIDA赠款正在进行中的14 几年前刚搬到纽约大学医学中心。 除了获得新能力的机会， 从我的新环境的独特研究潜力中获益， 研究计划的具体目标保持不变： 开发鼻吸剂滥用模型将提供技术 （1）允许评估相对滥用潜力， 溶剂和麻醉剂;（2）允许规范无毒 溶剂暴露水平和工业界的建议 暴露限值;（3）允许比较 吸入剂维持的药物寻求行为， 滥用其他药物维持的行为。 拟议的方案将分两个平行阶段进行： 1)猴溶剂自我给药。 专注- 将确定吸入剂的持续时间-效应曲线， 如烷基苯（例如甲苯）、酮和脂肪醇。 将审查加固时间表，以确定 这些药剂作为防腐剂的有效性。 吸入血液浓度 将被确定。 2)吸入物质的厌恶性。 我们将产生 通过终止有毒吸入剂来保持性能。 最初的厌恶可能在决定一个人的行为中起着重要的作用。 滥用潜力 使挥发性材料令人厌恶的技术 是至关重要的，并可能直接影响到产品 公式化。 3)有机溶剂对性能的影响。 吸入物质 诱导行为毒性，可以通过使用 时间表控制的行为 浓度效应曲线 将获得几种试剂，以确定浓度 维持自我管理与那些影响 其他表演。 这有助于描述其药理学特征 曲线，以及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.