CLINICAL CIRCUITRY UNDERLYING METHAMPHETAMINE ADDICTION

甲基苯丙胺成瘾的临床循环

基本信息

批准号：
7689492
负责人：
Robert James Malcolm
金额：
$ 21.31万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7689492
关键词：
Abstinence Age Alcohol dependence Alcohols Amphetamines Amygdaloid structure Animals Basal Ganglia Behavior Brain Brain imaging Brain region Characteristics Clinical Cocaine Cocaine Abuse Collaborations Communities Condition Corpus striatum structure Coupled Cues Data Dependence Development Dorsal Economics Environment Epidemic Event Exposure to Extinction (Psychology)Female Fostering Functional Magnetic Resonance Imaging Growth Health Human Image Individual Inpatients Knowledge Learning Legal Literature Magnetic Resonance Imaging Maps Measures Memory Methamphetamine Methodology Neuroanatomy Neurobiology Nicotine Outpatients Pattern Personal Satisfaction 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 United States Ventral Striatum Visual Week Work addiction alcohol cue base blood oxygen level dependent cingulate cortex craving day drug craving drug development experience follow-up habit learning learning extinction male neural circuit neuroimaging pre-clinical preclinical study psychologic reinforcer relating to nervous system single photon emission computed tomography therapy development tool

项目摘要

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) 依赖会对心理和身体产生严重后果健康，并给社区带来巨大的经济和法律负担。长期滥用冰毒和依赖冰毒西方的一个严重问题，现在正以接近流行病的程度蔓延到美国东部过去五年来，南卡罗来纳州经历了巨大的增长。提示引发的药物渴望是据信，这是在自然环境中寻求毒品和复发的关键组成部分。调查员表明成瘾的一个关键特征是线索显着性的增加和线索药物的增强记忆回路压倒了前额皮质通常对自然线索施加的抑制控制和强化物。冰毒治疗的药物开发正在取得进展，但仍有许多工作要做了解冰毒成瘾的基本神经生物学。线索曝光与功能相结合神经影像技术（PET、SPECT、fMRI）在阐明大脑回路方面非常有用尼古丁、可卡因和酒精依赖者。有人建议，确定药理学通过功能性脑成像测量，改变人类线索诱发的渴望和药物寻求的药物很可能成为潜在药物治疗剂的有效筛选工具和有效的途径药物开发。在临床前模型或人类临床成像中，不存在 METH 提示激活的电路图。对啮齿动物的临床前研究表明，经过冰毒治疗的动物可能会损害灭绝学习能力。我们的小组使用功能磁共振成像技术来评估酒精引起的区域脑回路变化，最近，可卡因提示刺激。与项目 #1 密切合作，该项目的主要目标是建议开发程序，在提示生成的条件下通过功能磁共振成像评估大脑回路非寻求治疗的冰毒依赖者的渴望和提示消失。使用 BOLD fMRI，多个随着时间的推移，功能磁共振成像将被评估，以测量暴露于冰毒线索和环路激活的变化。中性线索。我们建议招募 60 名非寻求治疗的冰毒依赖男性和女性年龄在 18 岁至 50 岁之间的民族和种族群体参与这项研究。这项研究将包括 3 阶段：1）门诊筛查； 2) 住院患者在 METH 期间进行重复 fMRI 提示暴露，以及中性提示暴露； 3) 两周的门诊随访。该项目将与Project密切合作 #4 开发 METH 特定的环境线索，并与项目 #1 一起确定特定的环境线索冰毒提示反应和消退的潜在电路。之间的双向信息交换识别参与这些重要功能的关键电路的人类和动物研究将加快发现的步伐。