Translational Research on Prescription Drug Abuse

说明(申请人提供)：本建议书是根据RFA-DA-08-022的要求提交的。我们的总体目标是发展一个多学科的P20研究中心，对处方药滥用的神经生物学和分子机制进行基础科学和临床研究。尽管处方药成瘾与非法药物成瘾有许多相似的特征，但处方药滥用在合法医疗使用的背景下是一种独特的药物成瘾形式，有待调查。事实上，近年来人们对处方药滥用的担忧与日俱增。因此，建立一个完全致力于这一领域的翻译研究中心将是新颖、及时和具有临床意义的。在拟建的P20中心的科研计划中，我们将研究阿片类镇痛剂成瘾的神经影像和分子机制，以及它与临床和实验疼痛的相互作用。整个研究计划将提出三个具体目标：1)检测与人类受试者和啮齿动物疼痛和阿片成瘾相互作用有关的行为和神经影像变化，2)探索大脑多巴胺系统在疼痛和阿片成瘾相互作用中的作用，以及3)研究脑多巴胺受体在疼痛和阿片成瘾相互作用中作用的分子机制。这项研究计划产生的数据将为阿片成瘾的神经和分子机制及其与临床疼痛的相互作用提供新的信息。这个P20中心的运营计划将包括短期和长期目标。这个P20中心的短期目标是1)发展和巩固基础设施，2)促进跨学科、协作的基础科学和临床研究，3)根据拟议的具体目标产生科学数据。长期目标是1)为未来的P50研究中心准备后勤和管理需求，2)为P50研究中心下的未来研究产生初步数据。为这个P20中心勾勒的研究和操作计划的成功实施将导致形成一个多学科的P50研究中心，扩大研究目标，研究处方药滥用的临床神经生物学和分子机制。

DESCRIPTION (provided by applicant): This proposal is submitted in response to RFA-DA-08-022. Our overall goal is to develop a multidisciplinary P20 research center that conducts basic science and clinical research on the neurobiology and molecular mechanisms of prescription drug abuse. Although addiction to prescription drugs and illicit drugs has many similar features, prescription drug abuse in the setting of legitimate medical use is a unique form of drug addiction that remains to be investigated. Indeed, significant concerns over prescription drug abuse have grown over recent years. Therefore, establishing a translational research center entirely dedicated to this line of research will be novel, timely and clinically relevant. In the scientific research plan of the proposed P20 center, we will study neuroimaging and molecular mechanisms of addiction to opioid analgesics and its interaction with clinical and experimental pain. Three specific aims will be proposed for the overall research plan: 1) to examine behavioral and neuroimaging changes in relation to the interaction between pain and opioid addiction in human subjects and rodents, 2) to explore the role of the brain dopaminergic system in the interaction between pain and opioid addiction, and 3) to investigate the molecular mechanisms underlying the functional role of brain dopamine receptors in the interaction between pain and opioid addiction. The data generated from this research plan will provide novel information on the neural and molecular mechanisms of opioid addiction and its interaction with clinical pain. The operational plan of this P20 center will include both short-term and long-term goals. The short-term goals of this P20 center are to 1) develop and consolidate infrastructures, 2) foster interdisciplinary, collaborative basic science and clinical research, and 3) generate scientific data according to proposed specific aims. The long-term goals are to 1) prepare logistic and administrative needs for the future P50 research center and 2) generate preliminary data for future studies under the P50 research center. The successful implementation of the research and operational plan outlined for this P20 center will lead to the formation of a multidisciplinary P50 research center with expanded research objectives to study the clinical neurobiology and molecular mechanisms of prescription drug abuse.