Methamphetamine Abuse, Inhibitory Control: Implications for Treatment

甲基苯丙胺滥用、抑制控制：对治疗的影响

• 批准号: 7294351
• 负责人: Edythe Danick London
• 金额: $ 70.28万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294351
• 关键词: Methamphetamine; Abuse; Inhibitory; Control; Implications

DESCRIPTION (provided by applicant): Despite advances in the scientific understanding of drug abuse and dependence, effective treatments are lacking, and new therapies for these disorders are urgently needed. The proposed P20- funded Developmental Center for Translational Research on Addictions will address this need by integrating preclinical studies to directly inform clinical research on drug addiction, and complementarily, leveraging clinical insights to help target basic science approaches. The proposed Center links basic scientists who have made significant contributions to knowledge of the neurobiological components of addiction with clinical investigators who are at the forefront in treatment research. The theme of the developmental center will be impaired inhibitory control as a therapeutic target for methamphetamine (MA) dependence. We made this choice because of: a) the magnitude of the MA abuse problem worldwide; b) the severity of its consequences; c) the lack of an effective treatment for MA dependence; d) the importance of impaired inhibitory control to drug addiction; and e) our leadership in advancing the understanding and treatment of MA abuse. With this initial focus, we propose four interrelated projects to characterize impairments in response inhibition consequent to methamphetamine (MA) exposure at behavioral, neural systems, and neurochemical levels in both human and animal models, and to assess the pharmacological modulation of these deficits. The four research projects in this P20 Center aim: 1) to delineate the neural circuitry underlying deficits in inhibitory control in MA-dependent human subjects; 2) to relate deficits in inhibitory control to drug-taking behavior using a human laboratory model of MA self administration; 3) to establish and characterize (behaviorally and neurochemically) a non-human primate model for investigating inhibitory control deficits characteristic of MA abuse; and 4) to characterize regional brain neurochemical effects of pharmacological manipulations aimed at modulating response inhibition in a rodent model for MA dependence. The four projects are integrated in a way that would not be feasible if each project had been designed to be a discrete study, outside the Center environment. The Center will support these scientific projects with the over-arching goals of creating an environment for interdisciplinary translational research, whereby the flow of information from basic research in animal models and human laboratory studies can be rapidly applied to development of treatments for drug abuse, and developing a program of research career development that will coordinate and enhance existing training programs, providing multiple, excellent opportunities for pre- and postdoctoral fellows and faculty to initiate new projects focusing on translational approaches to studies of the neurobiology of drug abuse.

描述（由申请人提供）：尽管在药物滥用和依赖的科学认识方面取得了进展，但缺乏有效的治疗方法，迫切需要针对这些疾病的新疗法。拟议的P20资助的成瘾转化研究发展中心将通过整合临床前研究来解决这一需求，以直接为药物成瘾的临床研究提供信息，并补充利用临床见解来帮助瞄准基础科学方法。该中心将为成瘾的神经生物学成分知识做出重大贡献的基础科学家与处于治疗研究前沿的临床研究人员联系起来。发展中心的主题将是受损的抑制控制作为甲基苯丙胺（MA）依赖的治疗靶点。我们做出这一选择是因为：a）MA滥用问题在全球范围内的严重性; B）其后果的严重性; c）缺乏有效的MA依赖治疗; d）抑制控制受损对药物成瘾的重要性;以及e）我们在推进MA滥用的理解和治疗方面的领导地位。有了这个最初的重点，我们提出了四个相互关联的项目来表征甲基苯丙胺（MA）暴露在人类和动物模型的行为，神经系统和神经化学水平的反应抑制损伤，并评估这些赤字的药理学调制。该P20中心的四个研究项目旨在：1）描绘MA依赖人类受试者抑制控制缺陷的神经回路; 2）使用MA自我给药的人类实验室模型将抑制控制缺陷与吸毒行为联系起来;（3）建立和表征（行为学和神经化学）用于研究MA滥用特征性抑制性控制缺陷的非人灵长类动物模型;和4）表征旨在调节MA依赖性啮齿动物模型中的反应抑制的药理学操作的局部脑神经化学作用。如果每个项目都被设计为中心环境之外的独立研究，则这四个项目的整合方式是不可行的。该中心将支持这些科学项目，其目标是为跨学科转化研究创造一个环境，从而使动物模型和人类实验室研究的基础研究信息流能够迅速应用于药物滥用治疗的开发，并制定一项研究职业发展计划，以协调和加强现有的培训计划，提供多种，为博士前和博士后研究员和教师提供了极好的机会，以启动新的项目，重点是药物滥用神经生物学研究的转化方法。