STIMULUS PROPERTIES OF ANXIOLYTICS IN HUMANS

在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，这些变量有助于 地西潘的增强作用及其判别性研究 安定的刺激(DS)特性和主观效应。在以前的 由首席调查员进行的研究，安定一般 不起到积极增强剂的作用。然而，最近的两项研究 结果表明，在一定的温度和温度下，可以提高其增强性能。 涉及多次给药的环境条件 社交环境中的剂量，特别是有病史的参与者 大量饮酒的原因。其他偏好研究，包括 安定的设计是为了确定其他行为和 安定选择的药理学变量。一系列研究将 考察分次给药、药物预处理、社会干预的作用 促进。此外，未使用的刺激性药物(如马吲哚) 在之前的研究中自我管理将在类似的情况下进行评估 确定加固是否具有修改能力的条件 特性可推广到其他类别的药物。另一项研究 将研究其他可同时获得的增强剂对 地西潘的增强作用在两组受试者中都有 有少量和重度饮酒的历史。关于DS的研究 安定的作用是人类研究的延伸 受过区分10毫克d-苯丙胺和安慰剂的训练。在这些 受过训练的个体，发现某些厌食药物 被区别为苯丙胺而不同的厌食剂 从药理上讲，苯丙胺(如芬氟拉明)不起作用。因为一个 来自不同药理类别的药物也不能替代，这些 结果表明，这种鉴别是药理学上的特异性。 本申请中所述的药物歧视研究如下 旨在评估用于培训 安非他明作为训练药物与安非他命的辨别 确定：其药理特异性；个体是否患有 焦虑等先前存在的特征显示出不同 敏感度或选择性；以及诸如指令或 行为史可以改变抗焦虑药物的DS特性。已被占用 综上所述，这两系列研究将增加我们对 抗焦虑药物的刺激作用与其依赖性 潜在的和治疗上的用处，以及提供更一般的 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.