STIMULUS PROPERTIES OF ANXIOLYTICS IN HUMANS

本申请中提出的研究的目的是进一步 描述行为和药理学变量，有助于 地西泮的增强特性，并研究区分 地西泮的刺激（DS）特性和主观效应。 前几 在主要研究者进行的研究中，地西泮通常 没有起到积极的促进作用。 然而，最近的两项研究 表明，其增强性能可以增加下 环境条件涉及多次给药 在社会环境中的剂量，特别是在有病史的参与者中 酒精消耗量更大。 其他偏好研究， 地西泮的目的是确定其他行为和 地西泮选择的药理学变量。 一系列研究将 检查分次给药、药物预处理、社会 便利化 此外，刺激性药物（例如，马吲哚）， 将在类似条件下评价既往研究中的自我给药 条件，以确定是否有能力修改增强 这些特性可推广到其他种类的药物。 另一项研究 将研究其他同时可用的替代品对 地西泮的强化特性，无论是在参与者与 轻度和重度饮酒史。 关于DS的研究 地西泮的功能是人类研究的延伸， 接受过区分10毫克右旋苯丙胺和安慰剂的训练。 在这些 经过训练的人，发现某些厌食药物 区别为安非他明，而厌食剂， 从安非他明中提取的药物（例如，芬氟拉明）没有。 由于 来自不同药理学类别的药物也不能替代，这些 结果表明，这种歧视是特定的。 本申请中描述的药物辨别研究是 旨在评估用于培训 安非他明歧视，起诉地西泮作为训练药物， 确定：其药理学特异性;个体是否具有 先前存在的特征，如焦虑， 敏感性或选择性;以及诸如指令或 行为史可以改变抗焦虑药的DS性质。 采取 这两个系列的研究将增加我们对 抗焦虑药的刺激功能与其依赖性有关 潜在的和治疗的有用性，以及提供一个更普遍的 理解改变刺激的环境影响 药物在人体内的作用。

The aims of the research proposed in this application are to further delineate behavioral and pharmacological variables that contribute to the reinforcing properties of diazepam and to investigate the discriminative stimulus (DS) properties and subjective effects of diazepam. In previous studies conducted by the Principal Investigator, diazepam has generally not functioned as a positive reinforcer. However, two recent studies showed that its reinforcing properties could be increased under environmental conditions involving administering the drug in multiple doses in a social setting, particularly in participants who had a history of heavier alcohol consumption. Additional preference studies with diazepam are designed to determine the influence of other behavioral and pharmacological variables on diazepam choice. One series of studies will examine the role of divided dosing, pharmacological pretreatment, social facilitation. Further, stimulant drugs (e.g., mazindol) that were not self-administered in previous studies will be evaluated under similar conditions to determine whether the ability to modify reinforcing properties generalizes to other classes of drugs. An additional study will examine the influence of other concurrently available reinforcers on the reinforcing properties of diazepam, both in participants with histories of light and heavier alcohol consumption. The studies on the DS functions of diazepam are an extension of research in which humans were trained to discriminate 10 mg d-amphetamine from placebo. In these trained individuals, it was found that certain anorectic drugs were discriminated as amphetamine whereas anorectics which differed pharmacologically from amphetamine (e.g., fenfluramine) did not. Since a drug from a different pharmacological class also did not substitute, these results indicated that the discrimination was pharmacologically specific. The drug discrimination studies described in the present application are designed to assess the generality of the procedure used to train the amphetamine discrimination by suing diazepam as the training drug and determine: its pharmacological specificity; whether individuals with preexisting characteristics such as anxiety show differences in sensitivity or selectivity; and whether variables such as instructions or behavioral history can modify the DS properties of anxiolytics. Taken together, these two series of studies will increase our understanding of the stimulus functions of anxiolytics related to their dependence potential and therapeutic usefulness as well as provide a more general understanding of environmental influences that modify the stimulus functions of drugs in humans.