ANORECTIC DRUGS--ABUSE & BEHAVIORAL MECHANISMS OF ACTION

厌食药物——滥用

• 批准号: 3209318
• 负责人: Richard W Foltin
• 金额: $ 18.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3209318
• 关键词: anorexic agent; baboons; caloric dietary content; central nervous system stimulants; cholecystokinin; dextroamphetamine; diazepam; drug tolerance; eating; fasting; fenfluramine; nutrition related tag; operant conditionings; phencyclidine; psychopharmacology; sedative /hypnotic; weight control agent

There is increasing concern about the use and misuse of anorectic drugs, with more and more prescribed as adjuncts in weight control therapy. The present proposal will investigate the effects of these drugs on patterns of food intake in baboons maintained under minimal deprivation conditions. Food will be continuously available under an operant schedule that differentiates patterning of meals from pattern of pellet intake within meals. Schedule parameters will be chosen so that each animal will have control over initiation as well as termination of feeding throughout the day. Baseline patterns of food intake will be determined by measuring meal frequency, size, duration, and distribution of intake within each meal over several months. The effects of four manipulations on feeding will be assessed in order to compare those effects with later drug effects. Caloric prefeeding, acute deprivation cholecystokinin administration and the availability of an alternate energy source will all be parametrically manipulated. Complete dose-response functions for six amphetamine-like/stimulant anorectic drugs, three fenfluramine-like/sedative anorectic drugs and phenylpropanolamine will be determined. In addition, diazepam, known to increase food intake, and phencyclidine, which should decrease food intake by causing motor deficits, will also be tested. Profiles of the behavioral mechanisms of all these drugs when given on a single dose basis will be developed. Furthermore, the work will analyze the effects of long-term administration of low doses of d-amphetamine and fenfluramine on food intake; cross-tolerance to each other, phenylpropanolamine, and phencyclidine will be examined. The data collected in these studies will enhance the abuse liability data base of the anorectics and, in addition, provide important information about their behavioral mechanisms. This research will add to the large experimental data base on the self-administration of these compounds in primates, and provide important information for the analysis of the behavioral mechanisms of these drugs, e.g., effects on meal size and patterning. Such information will be useful both in evaluation of therapeutic efficacy and in understanding the basic processes involved in eating behavior.

人们越来越关注厌食药的使用和误用， 随着越来越多的人在体重控制治疗中被用作辅助药物。这个 目前的建议将调查这些药物对模式的影响 在最低限度的剥夺条件下，狒狒的摄食量保持不变。 食品将根据可操作的时间表持续供应， 区分膳食的模式和体内的颗粒摄入模式 一顿饭。将选择时间表参数，以便每只动物都有 在整个过程中对开始和终止喂食的控制 天。食物摄入量的基线模式将通过测量膳食来确定 每餐摄入量的频率、大小、持续时间和分布 几个月了。四种操作对喂食的影响将是 进行评估，以便将这些效果与后来的药物效果进行比较。 卡路里预喂养，急性剥夺CCK给药和 替代能源的可获得性将全部由参数决定 被操纵了。六个完整的剂量-反应函数 安非他明类/兴奋剂类厌食药物，三种 芬氟拉明类/镇静类厌食药和苯丙醇胺 下定决心。此外，已知可增加食物摄入量的安定，以及 苯环利定，它应该会导致运动障碍，从而减少食物的摄入量， 也将接受测试。所有这些行为机制的概况 将开发单次给药的药物。此外， 这项工作将分析长期服用低剂量药物的效果。 D-苯丙胺和芬氟拉明对食物摄入量的交叉耐受性 其他，苯丙醇胺和苯环利定将被检查。数据 这些研究所收集的资料，将会加强 厌食者，此外，还提供了关于其 行为机制。这项研究将增加大型实验 这些化合物在灵长类动物体内自我给药的数据库，以及 为行为机制的分析提供重要信息 在这些药物中，例如，对食物大小和图案的影响。是这样的 这些信息将有助于评估治疗效果和 了解饮食行为所涉及的基本过程。