Modeling Behavioral Treatments for Stimulant Abuse

模拟兴奋剂滥用的行为治疗

• 批准号: 6963138
• 负责人: MARK G LESAGE
• 金额: $ 16.16万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6963138
• 关键词: behavior modification; behavioral /social science research tag; buprenorphine; cocaine; combination therapy; drug /alcohol abstinence; drug abuse; drug abuse chemotherapy; drug abuse therapy; laboratory rat; nicotine; operant conditionings; psychological reinforcement; self medication

DESCRIPTION (provided by applicant): The purpose of this project is to examine the effects of alternative nondrug reinforcement on stimulant self-administration in rats. The long-term goal is to develop a model of reinforcement-based clinical interventions for stimulant abuse that can be used to examine techniques to increase the efficacy of such interventions and provide a clinically relevant platform for preclinical medications development. In animal models of drug abuse, the prominence of research on neuropharmacological mechanisms that mediate the reinforcing effects of stimulants has resulted in much less emphasis on the important role that environmental variables play in stimulant drug self-administration, as well as their role in modulating the efficacy of medications in reducing drug self-administration. Given the superior clinical efficacy of combining behavioral and pharmacological treatments, this relative lack of emphasis on environmental variables may limit the contributions of animal research to the development of more effective combined treatments for stimulant abuse. One of the most effective behavioral treatments for stimulant abuse is contingency management (CM), which involves delivery of alternative reinforcers contingent upon abstinence from drug use. In preliminary studies, novel preclinical models of CM interventions for drug abuse have been developed and shown to significantly reduce drug self-administration in rats. The primary model employs a differential-reinforcement-of-alternative-behavior (DRA) schedule of alternative nondrug reinforcement, in which availability of an alternative reinforcer (e.g., sucrose pellets) is made contingent upon abstinence from drug self-administration. Specific Aim #1 is to characterize this model further by examining the generality of the effects a DRA schedule of alternative nondrug reinforcement across different unit doses and types of stimulant (nicotine and cocaine) maintaining responding. Specific Aim #2 is to examine whether the extent of reduction produced by a DRA schedule is enhanced by environmental variables, such as magnitude of alternative reinforcement and presentation of stimuli paired with alternative reinforcement. Specific Aim #3 is to examine whether the extent of reduction is increased by combining the DRA schedule with pharmacological treatment. These studies should provide a useful preclinical model of CM interventions and be helpful in elucidating behavioral and pharmacological variables that could enhance their efficacy.

描述（由申请人提供）：该项目的目的是检查替代性非药物增强对大鼠刺激性自我给药的影响。长期的目标是开发一种基于增强的临床干预措施的模型，用于刺激性滥用，该模型可用于检查提高此类干预措施的功效的技术，并为临床上的临床前药物开发提供临床相关的平台。在药物滥用的动物模型中，介导刺激剂增强作用的神经药理机制的研究的突出导致对环境变量在刺激性药物自我给药中发挥作用的重要作用较少，以及它们在调节药物在减少药物自我自我促进中的功能中的作用。鉴于将行为和药理治疗结合起来的卓越临床功效，这种对环境变量的相对缺乏重视可能会限制动物研究对开发更有效的刺激滥用综合治疗方法的贡献。刺激性滥用的最有效的行为治疗之一是应急管理（CM），其中涉及替代加固剂的交付，包括禁止使用毒品。在初步研究中，已经开发了用于药物滥用的CM干预措施的新型临床前模型，并证明可以显着降低大鼠药物自我给药。主要模型采用替代性nondrug钢筋的差异性 - 强化 - 替代方案（DRA），其中替代增强剂的可用性（例如蔗糖颗粒）取决于对药物自我给药的禁欲。具体目的＃1是通过检查效果的一般性进一步表征该模型，以跨不同单位剂量和类型的兴奋剂（尼古丁和可卡因）维持响应的替代性nondrug加固的DRA时间表。具体目的＃2是检查DRA时间表产生的还原程度是否通过环境变量增强，例如替代增强的幅度和与替代增强的刺激的呈现。特定目标＃3是通过将DRA时间表与药理治疗相结合，是否会检查减少程度是否增加。这些研究应提供CM干预措施的有用的临床前模型，并有助于阐明行为和药理学变量，以提高其疗效。