CLINICAL CIRCUITRY UNDERLYING METHAMPHETAMINE ADDICTION

甲基苯丙胺成瘾的临床循环

• 批准号: 7922076
• 负责人: Robert James Malcolm
• 金额: $ 21.02万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7922076
• 关键词: Abstinence; Age; Alcohol dependence; Alcohols; Amphetamines; Amygdaloid structure; Animals; Basal Ganglia; Behavior; Brain; Brain imaging; Brain region; Characteristics; Clinical; Cocaine; Collaborations; Communities; Corpus striatum structure; Coupled; Cues; Data; Dependence; Development; Dorsal; Economics; Environment; Epidemic; Event; Exposure to; Extinction (Psychology); Female; Fostering; Functional Magnetic Resonance Imaging; Growth; Human; Image; Individual; Inpatients; Knowledge; Learning; Legal; Literature; Magnetic Resonance Imaging; Maps; Measures; Memory; Methamphetamine; Methodology; Neuroanatomy; Neurobiology; Nicotine; Outpatients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Phase; Positron-Emission Tomography; Pre-Clinical Model; Prefrontal Cortex; Procedures; Process; Publishing; Race; Recruitment Activity; Relapse; Research Personnel; Resistance; Rodent; Role; Scanning; Screening procedure; Self Administration; South Carolina; Stress; Substance of Abuse; Techniques; Technology; Time; Translational Research; United States; Ventral Striatum; Visual; Work; addiction; alcohol cue; base; blood oxygen level dependent; cingulate cortex; craving; cue reactivity; drug craving; drug development; experience; follow-up; habit learning; learning extinction; male; methamphetamine abuse; neural circuit; neuroimaging; physical conditioning; pre-clinical; preclinical study; psychologic; reinforcer; relating to nervous system; single photon emission computed tomography; therapy development; tool

Methamphetamine (METH) dependence has drastic consequences in terms of psychological and physical health, and places great economic and legal burdens on communities. METH abuse and dependence, long a serious problem in the West, is now spreading in near-epidemic proportions to the eastern United States and has experienced dramatic growth in South Carolina in the past five years. Cue-elicited drug craving is believed to be a critical component in drug seeking, and relapse in the natural environment. Investigators have suggested that a critical characteristic of addiction is increased cue saliency and enhanced cue-drug memory circuits which overwhelm inhibitory control normally exerted by the prefrontal cortex for natural cues and reinforcers. Medication development for METH treatment is progressing, but much remains to be learned about the fundamental neurobiology of METH addiction. Cue exposure coupled with functional neuroimaging techniques (PET, SPECT, fMRI) has been extremely useful in elucidating brain circuitry for nicotine, cocaine, and alcohol-dependent individuals. It has been suggested that identifying pharmacologic agents that alter human cue-induced craving and drug-seeking as measured with functional brain imaging could well be an effective screening tool for potential pharmacotherapeutic agents and a productive path for drug development. No circuitry map exists for METH cue activation in either preclinical models or human clinical imaging. Preclinical studies in rodents indicate that METH-treated animals may have impaired extinction learning. Our group has used the technique of fMRI to evaluate regional brain circuitry changes with alcohol and, more recently, cocaine cue stimulation. Working in close concert with Project #1, the primary aims of this proposal are to develop procedures to assess brain circuitry through fMRI under conditions of cue-generated craving and cue extinction in non-treatment-seeking METH-dependent subjects. Using BOLD fMRI, multiple fMRIs will be assessed over time to measure changes in circuit activation with exposure to METH cues and neutral cues. We propose to recruit 60 non-treatment-seeking METH-dependent males and females of all ethnic and racial groups between ages 18 and 50 to participate in this study. This study will consist of 3 phases: 1) outpatient screening; 2) inpatient cue-exposure with repeated fMRIs overtime during METH and neutral cue exposure; and 3) Two weeks of outpatient follow-up. This project will work closely with Project #4 in the development of METH-specific environmental cues and with Project #1 in identifying specific circuits underlying METH cue-reactivity and extinction. The bidirectional exchange of information between human and animal studies in identifying the critical circuitry involved in these important functions will accelerate the pace of discovery.

甲基苯丙胺（METH）依赖性在心理和身体方面产生了巨大后果 健康，并给社区带来巨大的经济和法律负担。滥用和依赖，长期 西方一个严重的问题现在正在以几乎流动的比例传播到美国东部 在过去的五年中，南卡罗来纳州经历了巨大的增长。提示引用的毒品渴望是 被认为是寻求药物和自然环境中复发的关键组成部分。调查人员 已经表明，成瘾的关键特征是提高提示显着性并提高了提示毒品 抑制抑制性控制的记忆电路通常由天然提示前额叶皮层施加 和增强剂。冰毒治疗的药物开发正在进行中，但仍有很多要 了解了甲基化成瘾的基本神经生物学。提示暴露与功能 神经影像技术（PET，SPECT，fMRI）在阐明脑电路方面非常有用 尼古丁，可卡因和依赖酒精的个体。有人建议识别药理学 用功能性脑成像测量的改变人提示引起的渴望和寻求药物的药物 很可能是潜在药物治疗剂的有效筛选工具，也是一种生产性途径 药物开发。 在临床前模型或人类临床成像中，甲基甲酸酯提示激活都不存在电路图。 啮齿动物中的临床前研究表明，经过甲基苯甲酸酯处理的动物可能会损害灭绝学习。 我们的小组使用fMRI技术来评估与酒精和，，， 最近，可卡因提示刺激。与Project＃1的密切音乐会合作，这是主要目的 建议是在提示生成的条件下制定通过fMRI评估脑电路的程序 在非治疗依赖METH的受试者中渴望和提示灭绝。使用大胆fMRI，多个 随着时间的推移，将评估FMRIS，以测量电路激活的变化，并暴露于甲基苯丙胺线索和 中性提示。我们建议招募60种非治疗依赖甲基苯丙胺的男性和女性 在18至50岁之间的种族和种族群体参加这项研究。这项研究将包括3个 阶段：1）门诊筛查； 2）在甲基甲基苯丙胺和 中性提示暴露； 3）两周的门诊随访。该项目将与项目紧密合作 ＃4在开发甲基苯丙胺特异性环境提示和项目＃1中识别特定的 甲基反应性和灭绝的基础电路。之间的双向交换 人类和动物研究在识别这些重要功能涉及的关键电路时将 加速发现的速度。