Cholinergic Involvement in ADHD and Substance Abuse

胆碱能参与多动症和药物滥用

• 批准号: 6710323
• 负责人: David J Bucci
• 金额: $ 4.72万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6710323
• 关键词: attention deficit disorder; behavior; clinical research; cognition; cooperative study; human subject; laboratory rat; motivation; nicotine; performance; psychopharmacology; reinforcer; substance abuse related disorder

DESCRIPTION (provided by applicant): Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood psychological disorders, occurring in as many as 3-5% of children. The symptoms of ADHD, including inattention, restlessness, impulsivity, and hyperactivity, often lead to significant difficulties in functioning. Dysfunction of central dopaminergic and noradrenergic systems is thought to play a major role in producing this impairment. A recent clinical study by members of our group provides preliminary evidence that nicotine treatment ameliorates the deficits in behavioral inhibition in adolescents suffering from ADHD. Interestingly, adolescents with ADHD are twice as likely to become cigarette smokers and tobacco users as those without ADHD, a trend that continues into adulthood. The positive effects of nicotine on cognitive processing and inhibition may contribute to the higher risk of chronic tobacco use/abuse. At the present time, the reasons underlying the vulnerability of individuals with ADHD to use/abuse tobacco are poorly understood, as are the neurobiological mechanisms by which nicotine exerts its beneficial effects. To fill this gap in the existing literature, this R21 application will develop a research partnership between existing basic and clinical investigators to explore the role of cholinergic systems in the cognitive and behavioral symptomatology of ADHD and possible links to substance abuse. Basic studies of the behavioral and neurobiological mechanisms of cholinergic involvement related to ADHD will have direct bearing on clinical research by 1) providing additional insight into the etiology of ADHD, 2) improving the characterization of behavioral and neurochemical deficits associated with this disorder, 3) guiding future drug development (e.g., cholinergic therapies), and 4) facilitating the identification of individuals who may be at high risk for substance abuse. Consistent with the recent recommendations of the National Advisory Mental Health Council Behavioral Science Workgroup (2000), the primary outcome of our collaboration will be the development of a coherent Translational Research Agenda to develop this area of research. In addition, the proposed activities will generate valuable preliminary data for subsequent full-scale studies and preparation of follow-up research applications (e.g., R01, R24).

描述（由申请人提供）： 注意力缺陷/多动症 (ADHD) 是最常见的儿童心理障碍之一，有多达 3-5% 的儿童患有这种疾病。 ADHD 的症状包括注意力不集中、烦躁不安、冲动和多动，通常会导致严重的功能困难。中枢多巴胺能和去甲肾上腺素能系统的功能障碍被认为是造成这种损伤的主要原因。我们小组成员最近进行的一项临床研究提供了初步证据，表明尼古丁治疗可以改善患有多动症的青少年的行为抑制缺陷。有趣的是，患有多动症的青少年吸烟和吸烟的可能性是没有多动症的青少年的两倍，这一趋势一直持续到成年。尼古丁对认知处理和抑制的积极作用可能会导致慢性烟草使用/滥用的风险较高。目前，人们对多动症患者容易使用/滥用烟草的原因知之甚少，尼古丁发挥其有益作用的神经生物学机制也是如此。为了填补现有文献中的这一空白，该 R21 申请将在现有基础研究人员和临床研究人员之间建立研究伙伴关系，以探索胆碱能系统在 ADHD 认知和行为症状学中的作用以及与药物滥用的可能联系。与 ADHD 相关的胆碱能参与的行为和神经生物学机制的基础研究将对临床研究产生直接影响：1）提供对 ADHD 病因的更多见解，2）改善与这种疾病相关的行为和神经化学缺陷的特征，3）指导未来的药物开发（例如胆碱能治疗），4）促进识别可能处于这种状态的个体。 药物滥用的高风险。根据国家心理健康咨询委员会行为科学工作组 (2000) 最近的建议，我们合作的主要成果将是制定一个连贯的转化研究议程来发展这一研究领域。此外，拟议的活动将为后续全面研究和后续研究应用的准备（例如，R01、R24）产生有价值的初步数据。