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: 3210612
• 负责人: BARBARA E SLIFER
• 金额: $ 7.06万
• 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 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3210612
• 关键词: behavior test; central nervous system stimulants; cocaine; dextroamphetamine; discrimination learning; dosage; drug addiction; drug administration rate /duration; drug tolerance; drug withdrawal; laboratory rat; 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.

这项建议是为了检查慢性疾病所产生的依赖 用大鼠行为学模型给药可卡因 依赖。可卡因滥用在过去几年中显著增加 过去的十年反映在个人数量的增加上 寻求与可卡因相关的医疗和行为方面的帮助 有问题。这些增长反过来又突显了 缺乏关于可卡因滥用和依赖的数据 潜在的治疗方法。科学与通俗 社区都开始认识到强烈的依赖 药物的责任，然而，还有很多东西需要了解 关于对可卡因的依赖。这 该提案包括开发一种啮齿动物模型 使用操纵性行为来量化药物的影响 给药和戒毒。这样的模式将允许 操纵可能涉及到的多个变量 可卡因依赖。可卡因的完整特征 依赖将包括确定禁欲的性质 证候，以及用药剂量和用药时间的关系 政府对戒断的严重程度。的影响 可卡因依赖期间的各种药物干预 将对撤药进行研究，以确定与 其他化合物和潜在的治疗干预措施。 此外，基本的神经药物操作包括 使用选择性激动剂和拮抗剂将用于 确定多巴胺的相对贡献， 可卡因依赖中的去甲肾上腺素和5-羟色胺系统。 这项建议中的研究还将评估环境 贡献，如增援计划、类型 对发展的偶然性和刺激控制程度 对可卡因的耐受性和依赖性。可卡因的影响 以离散推注的方式提供的注射将与 缓慢、持续输注的药物的效果。这个 这项拟议项目中概述的研究将提供a)一种啮齿动物 评估戒毒情况的模型，即使在没有 可观察到的影响，b)有助于我们的重要信息 了解可卡因耐受性和依赖性的性质以及c) 关于可能调节神经化学系统的信息 耐受性和依赖性，暗示着潜在的心理治疗 治疗可卡因戒断和依赖的方法。