BEHAVIORAL ANALYSIS OF TOLERANCE AND DEPENDENCE: COCAINE

耐受性和依赖性的行为分析：可卡因

• 批准号: 3210610
• 负责人: BARBARA E SLIFER
• 金额: $ 9.16万
• 依托单位: UNIVERSITY OF NEW ORLEANS
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3210610
• 关键词: behavior test; central nervous system stimulants; cocaine; dextroamphetamine; discrimination learning; dosage; drug addiction; drug administration rate /duration; drug tolerance; drug withdrawal; neurochemistry; operant conditionings; pharmacokinetics; phencyclidine; psychological reinforcement; psychopharmacology; stimulus generalization; sympathetic nervous system

This proposal is to examine the dependence produced by chronic cocaine administration using a rat model of behavioral dependence. The significant increases in cocaine abuse over the past decade is reflected in the increased numbers of individuals seeking help with cocaine related medical and behavioral problems. These increases have, in turn, served to emphasize the paucity of data concerning cocaine abuse and dependence and potential treatment approaches. The scientific and lay community alike have come to recognize the powerful dependence liability of the drug, however there is much to be learned concerning the dependence which occurs to cocaine. This proposal includes the development of a rodent model of dependence using operant behavior to quantify the effects of drug administration and drug withdrawal. Such a model will allow the manipulation of a number of variables which may be involved in cocaine dependence. Complete characterization of cocaine dependence will include determining, the nature of the abstinence syndrome, and the relationship of dose and duration of drug administration on the severity of withdrawal. The effects of various pharmacological interventions during cocaine dependence and withdrawal will be studied to determine cross-tolerance with other compounds and potential therapeutic interventions. Additionally, basic neuropharmacological manipulations involving the use of selective agonists and antagonists will be used to determine the relative contributions of the dopamine, norepinephrine, and serotonin systems in cocaine dependence. The research in this proposal will also assess the environmental contributions such as the schedule of reinforcement, type of contingencies and degree of stimulus control to the development of tolerance and dependence on cocaine. The effects of cocaine delivered as discrete bolus injections will be compared to the effects of the drug delivered as a slow, continuous infusion. The research outlined in this proposed project will provide a) a rodent model for assessing drug abstinence, even in the absence of observable effects, b) important information which will help us understand the nature of cocaine tolerance and dependence and c) information on neurochemical systems which may mediate tolerance and dependence, suggesting potential psychotherapeutic approaches to treatment of cocaine abstinence and dependence.

这个建议是为了检查慢性药物依赖性 可卡因管理使用大鼠模型的行为 依赖 2000年至2005年期间可卡因滥用的显著增加， 在过去的十年里，越来越多的人 寻求与可卡因相关的医疗和行为帮助 问题 这些增长反过来又强调了 缺乏关于可卡因滥用和依赖的数据， 潜在的治疗方法。 科学与世俗 社会都开始认识到 药物的责任，但是有很多东西要学习 关于对可卡因的依赖。 这 建议包括开发一种啮齿动物模型， 使用操作行为来量化药物效应的依赖性 给药和停药。 这种模式将允许 操纵一些可能涉及的变量， 可卡因依赖 可卡因的完整特征 依赖性将包括确定，禁欲的性质 证候及用药量与时间的关系 根据戒断的严重程度给药。 的影响 可卡因依赖期间的各种药物干预 将研究和撤回，以确定交叉耐受性 其他化合物和潜在的治疗干预。 此外，基本的神经药理学操作， 选择性激动剂和拮抗剂的使用将用于 确定多巴胺的相对贡献， 去甲肾上腺素和血清素系统在可卡因依赖中的作用。 本提案中的研究还将评估环境 贡献，如加固时间表，类型 突发事件和发展刺激控制程度 对可卡因的耐受和依赖 可卡因的影响 作为离散推注输送的药物将与 缓慢、连续输注的药物效果。 的 这项拟议项目中概述的研究将提供a）一种啮齿动物 评估药物戒断的模型，即使在没有 可观察到的效果，B）重要的信息，这将有助于我们 理解可卡因耐受性和依赖性的性质; c） 关于可能介导的神经化学系统的信息 耐受性和依赖性，这表明潜在的心理治疗 可卡因戒断和依赖的治疗方法。