PET Studies of Amphetamine Treatment of ADHD

安非他明治疗 ADHD 的 PET 研究

• 批准号: 8429516
• 负责人: GEORGE A RICAURTE
• 金额: $ 50.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429516
• 关键词: Acute; Adult; Affect; Age; Amphetamines; Animals; Attention deficit hyperactivity disorder; Binding; Brain; Child; Control Groups; Corpus striatum structure; Coupled; Data; Diagnosis; Disease; Dopamine; Dose; Drug Administration Schedule; Elements; Functional disorder; Gender; Goals; Human; Image; Individual; Label; Life; Light; Measures; Methylphenidate; Narcolepsy; Papio; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Plasma; Positron-Emission Tomography; Presynaptic Terminals; Public Health; Reporting; Research; Risk; Role; Saimiri; Simulate; Symptoms; base; density; dopamine system; dopamine transporter; dopaminergic neuron; neuropsychiatry; neurotoxic; neurotoxicity; nonhuman primate; pre-clinical; psychostimulant; radioligand; vesicular monoamine transporter; vesicular monoamine transporter 2

Project Description Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neuropsychiatric disorder, affecting 3-5% of children and 1-5% of adults. Nearly 60% of adults who are diagnosed with ADHD report that they have been treated with medications, generally psychostimulants. One of the most common stimulants used to treat ADHD is amphetamine. Amphetamine has recently been shown to have the potential to destroy dopamine (DA) axon terminals in the brain of non-human primates (baboons and squirrel monkeys) at plasma concentrations similar to those that develop in ADHD patients. In these studies, amphetamine was given orally according to a schedule of drug administration that simulated the use of amphetamine in ADHD treatment. These preclinical observations, coupled with preliminary results indicating that adult ADHD patients previously treated with amphetamine have decrements [11] WIN 35,428-labeled binding potential (BP) that are unlikely to be related to acute effects of amphetamine on the DAT, raise concern that amphetamine treatment of adult ADHD may be associated with a risk of brain dopamine neurotoxicity. The purpose of the proposed research is to determine if the use of amphetamine for the treatment of adult ADHD is associated with a risk of brain dopaminergic neurotoxicity. To this end, positron emission tomography (PET) will be used to measure two structural elements of brain DA axon terminals, the DAT and the vesicular monoamine transporter-type 2 (VMAT-2), in adult ADHD patients previously treated with amphetamine. Findings in this group will be compared to those three other groups: 1) Adults with ADHD who have never received pharmacological treatment for ADHD; 2) Adults with ADHD who have been treated with methylphenidate, which is known to lack DA neurotoxic potential; and 3) Age- and gender- matched healthy adults never treated with psychostimulants. All subjects will be adults between the ages of 18 and 40 who have been free of CNS-active drugs (including prescribed stimulants) for at least two weeks (approximately 30 half-lives of amphetamine) prior to PET imaging. We hypothesize that adult, drug-free ADHD patients who have been previously treated with amphetamine will have lasting decreases in the DAT and VMAT-2 compared to all three control groups. If our hypothesis is correct, findings will have broad public health implications for the treatment of ADHD. Findings from this research should also shed additional light on the role of brain DA systems in the pathophysiology and symptoms of ADHD.

项目描述 注意力缺陷/多动障碍（ADHD）是一种高度流行的神经精神障碍， 影响3-5%的儿童和1-5%的成人。近60%被诊断患有ADHD的成年人报告说， 他们接受药物治疗，通常是精神兴奋剂。最常见的兴奋剂之一 用来治疗多动症的是安非他明 安非他明最近被证明具有破坏多巴胺（DA）轴突的潜力 血浆浓度下非人灵长类动物（狒狒和松鼠猴）脑中的终末 类似于多动症患者的症状。在这些研究中，安非他明是根据 一种模拟在ADHD治疗中使用安非他明的药物给药方案。这些 临床前观察，加上初步结果表明，成人ADHD患者以前 接受安非他明治疗后，结合潜力（BP）会下降[11] WIN 35，428-标记的结合潜力（BP）不太可能 与安非他明对DAT的急性作用有关，引起人们对安非他明治疗成人的关注， ADHD可能与脑多巴胺神经毒性的风险有关。 拟议研究的目的是确定使用安非他明治疗 成人ADHD与脑多巴胺能神经毒性的风险有关。为此，正电子发射 断层扫描（PET）将用于测量大脑DA轴突终末的两个结构要素，DAT和 囊泡单胺转运体2型（VMAT-2），在成人ADHD患者先前治疗， 安非他明这一组的发现将与其他三组进行比较：1）患有ADHD的成年人 从未接受过ADHD药物治疗的人; 2）接受过ADHD治疗的成人 与哌甲酯，这是已知的缺乏DA神经毒性潜力;和3）年龄和性别匹配 从未接受过精神兴奋剂治疗的健康成年人所有受试者均为18至40岁的成年人 至少两周内未使用CNS活性药物（包括处方兴奋剂） （大约30个安非他明半衰期）。 我们假设，成人，无药物ADHD患者谁曾接受过治疗， 与所有三个对照组相比，安非他明将具有DAT和VMAT-2的持续降低。如果我们的 假设是正确的，研究结果将对ADHD的治疗产生广泛的公共卫生影响。结果 这项研究还应该进一步阐明大脑DA系统在病理生理学中的作用， ADHD的症状