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: 7380003
• 负责人: Marc J Kaufman
• 金额: $ 10.16万
• 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/7380003
• 关键词: Abstinence; Acute; Address; Animal Model; Applications Grants; Behavioral; Blood Vessels; Brain; Cardiovascular system; Cerebrum; Chronic; Clinical; Cocaine; Collaborations; Controlled Study; Cross-Sectional Studies; Data; Development; Dose; Drug Exposure; Drug Kinetics; Drug abuse; End Point; Etiology; Female; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Goals; Gonadal Steroid Hormones; Grant; Hand; Heroin; Heroin Dependence; Hospitals; Human; Image; Independent Scientist Award; Interdisciplinary Study; Lead; Learning; Longitudinal Studies; Macaca mulatta; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maintenance; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolism; Methadone; Methods; Methylphenidate; Modeling; Monkeys; National Institute of Drug Abuse; Opiate Addiction; Opiates; Pharmaceutical Preparations; Phosphorus; Pliability; Principal Investigator; Recording of previous events; Research; Research Design; Research Personnel; Scientist; Self Administration; Self-Administered; Severities; Sex Characteristics; Spectrum Analysis; Substance abuse problem; Technology; Therapeutic; Time; Training; Treatment Efficacy; Treatment outcome; Universities; Wages; Work; base; career; cerebrovascular; desire; forest; human study; interest; multidisciplinary; neuroadaptation; neurochemistry; neuroimaging; next generation; nonhuman primate; programs; prospective; skills; steroid hormone analog; translational approach

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，使我能够投入 75% 以上的精力继续从事 3 个相互关联的项目。我是 NIDA R01 (DA 14674) 的新独立首席研究员，使用功能性 MRI (fMRI) 来阐明可卡因急性脑效应中性别差异的潜在机制。我是 NIDA R01（DA11231，PI：M. Pollack）分包合同的联合首席研究员，使用磷光谱（31p MRS）研究美沙酮维持的阿片依赖受试者的脑代谢。我是一项私人基金会资助的首席研究员，该资助将非人类灵长类动物慢性可卡因自我给药模型与磁共振 (MR) 技术相结合，以研究长期接触可卡因的大脑结构和功能影响。在获得 K01 奖期间，我通过研究可卡因和哌醋甲酯对大脑的急性影响，积累了临床 MR 成像方面的专业知识。我发现了脑血管对可卡因反应性的性别差异，这可能是慢性可卡因大脑影响中性别差异的基础。这项工作直接为我带来了 R01 资助。我还参与了对慢性可卡因、海洛因和多种药物滥用者的研究，这些研究导致了上述分包合同，并亲身了解了人类模型的混淆和局限性。这促使我寻求合作并筹集资金，使用非人类灵长类动物模型对受控慢性药物暴露进行前瞻性 MRI、MRS 和 fMRI 研究。我在猴子研究中的主要目标是确定累积的自我施用可卡因剂量与脑功能障碍严重程度（如人类研究所建议的）之间的关系，并确定急性药物作用如何导致慢性药物引起的脑功能障碍。这项工作是与维克森林大学的 Linda Porrino 博士合作完成的。 K02 奖将使我能够稳定和灵活地继续从事这些相互关联的项目。这种稳定性尤其重要，因为我运用在维克森林大学合作中学到的专业知识来开发方法和资金，在麦克莱恩医院的 4.0 Tesla 扫描仪和拟议的 9.4 Tesla 扫描仪上进行猴子高场 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有兴趣进行此类跨学科研究的下一代科学家，并将帮助我从新独立研究者过​​渡到独立研究者。

项目成果

Medial temporal lobe functioning and structure in the spontaneously hypertensive rat: comparison with Wistar-Kyoto normotensive and Wistar-Kyoto hypertensive strains.

• DOI: 10.1002/hipo.20681
• 发表时间: 2010-06
• 期刊: HIPPOCAMPUS
• 影响因子: 3.5
• 作者: Wells, Audrey M.;Janes, Amy C.;Liu, Xiaoxu;Deschepper, Christian F.;Kaufman, Marc J.;Kantak, Kathleen M.
• 通讯作者: Kantak, Kathleen M.