Chronic drug exposures in monkeys: serial MRI studies

猴子的慢性药物暴露：系列 MRI 研究

• 批准号: 7061621
• 负责人: Marc J Kaufman
• 金额: $ 9.29万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7061621
• 关键词: Macaca mulatta; bioimaging /biomedical imaging; brain disorders; brain imaging /visualization /scanning; brain metabolism; brain morphology; clinical research; cocaine; drug addiction; functional magnetic resonance imaging; gamma aminobutyrate; gender difference; hormone regulation /control mechanism; human subject; methadone; methylphenidate; morphometry; nuclear magnetic resonance spectroscopy; white matter; Macaca mulatta; bioimaging /biomedical imaging; brain disorders; brain imaging /visualization /scanning; brain metabolism; brain morphology; clinical research; cocaine; drug addiction; functional magnetic resonance imaging; gamma aminobutyrate; gender difference; hormone regulation /control mechanism; human subject; methadone; methylphenidate; morphometry; nuclear magnetic resonance spectroscopy; white matter

DESCRIPTION (provided by applicant): The aim of this program is to provide protected time to allow me to devote more than 75% of my effort to continue work on 3 interrelated projects. I am a newly independent Principal Investigator on a NIDA R01 (DA 14674) using functional MRI (fMRI) to elucidate mechanisms underlying sex differences in cocaine's acute brain effects. I am a co-Principal Investigator on a subcontract to a NIDA R01 (DA11231, PI: M. Pollack) using phosphorus spectroscopy (31p MRS) to study cerebral metabolism in methadone-maintained opiate dependent subjects. I am a Principal Investigator on a private foundation grant combining a nonhuman primate chronic cocaine self-administration model along with magnetic resonance (MR) technology to study brain structural and functional effects of chronic cocaine exposures. I developed expertise in clinical MR imaging during a K01 award by conducting studies of the acute brain effects of cocaine and methylphenidate. I identified sex differences in cerebrovascular reactivity to cocaine that may be bases for sex differences in chronic cocaine's brain effects. That work led directly to my R01 grant. I also collaborated on studies of chronic cocaine, heroin, and polydrug abusers that led to the subcontract noted above and learned first hand about confounds and limitations of human models. This led me to pursue collaborations and develop funding to conduct prospective MRI, MRS, and fMRI studies of controlled chronic drug exposures using non-human primate models. My primary goals in monkey studies are to identify relationships between cumulative self-administered cocaine dose and brain dysfunction severity (as suggested by human studies) and to determine how acute drug effects lead to chronic drug-induced brain dysfunction. This work is in collaboration with Dr. Linda Porrino at Wake Forest University. The K02 award will allow me stability and flexibility to continue work on these interrelated projects. This stability is particularly important as I apply expertise learned in my Wake Forest collaboration to develop methods and funding to conduct monkey high field MR studies on the McLean Hospital 4.0 Tesla scanner and on a proposed 9.4 Tesla scanner. The protected time offered by the K02 will allow me more time to train and mentor the next generation of scientists interested in conducting these types of interdisciplinary research, and will assist me in making the transition from newly independent to independent investigator.

描述（由申请人提供）： 该计划的目的是提供受保护的时间，以使我能够将超过75％的努力付诸实践，以继续在3个相互关联的项目上工作。我是使用功能性MRI（fMRI）的NIDA R01（DA 14674）的新独立的首席研究员，以阐明可卡因急性脑作用中性别差异的机制。我是使用磷光谱法（31p MRS）的NIDA R01（DA11231，PI：M. Pollack）分包合同的联合主管研究者，研究了美沙酮维持依赖性的受试者中的脑代谢。我是一名私人基金会赠款的首席研究员，结合了非人类灵长类动物慢性可卡因自我管理模型以及磁共振（MR）技术，以研究慢性可卡因暴露的大脑结构和功能效应。我通过对可卡因和哌醋甲酯的急性脑作用进行研究，在K01奖励期间开发了临床MR成像的专业知识。我确定了对可卡因的脑血管反应性的性别差异，这可能是慢性可卡因脑作用中性别差异的基础。这项工作直接导致了我的R01赠款。我还合作研究了慢性可卡因，海洛因和多药滥用者的研究，这些研究导致了上述分包合同，并亲自学习了人类模型的混杂和局限性。这促使我进行合作并开发资金，以使用非人类灵长类动物模型对受控的慢性药物暴露进行前瞻性MRI，MRS和功能磁共振成像研究。我在猴子研究中的主要目标是确定可卡因累积的可卡因剂量与脑功能障碍严重程度（如人类研究所建议）之间的关系，并确定急性药物作用如何导致长期导致慢性药物诱导的脑功能障碍。这项工作与Wake Forest University的Linda Porrino博士合作。 K02奖将使我能够稳定和灵活性继续从事这些相互关联的项目。这种稳定性尤其重要，因为我应用了Wake Forest合作中学到的专业知识来开发方法和资金，以在McLean Hospital 4.0 Tesla扫描仪和拟议的9.4 Tesla扫描仪上进行猴子高地MR研究。 K02提供的受保护时间将使我有更多时间来培训和指导下一代有兴趣进行这类跨学科研究的科学家，并将帮助我从新独立到独立研究者过​​渡。