Serotonergic changes in the frontal cortex during methamphetamine reinstatement

甲基苯丙胺恢复期间额叶皮质的血清素变化

• 批准号: 8700003
• 负责人: LISA M MCFADDEN
• 金额: $ 12.59万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700003
• 关键词: Area; Autopsy; Autoradiography; Award; Behavioral; Brain; Cognitive deficits; Collaborations; Commit; Corpus striatum structure; Data; Development; Dose; Drug Addiction; Drug abuse; Educational process of instructing; Environment; Equipment; Female; Foundations; Future Generations; Glutamates; Goals; Grant; Health; Hippocampus (Brain); Human; Image; Impulsive Behavior; Intake; Intervention; Laboratories; Learning; Measures; Medial; Mediating; Mentors; Methamphetamine; Methamphetamine dependence; Neurobehavioral Manifestations; Pathway interactions; Pharmaceutical Preparations; Pharmacotherapy; Play; Pre-Clinical Model; Prefrontal Cortex; Public Health; Rattus; Receptor Activation; Relapse; Reporting; Research; Research Personnel; Research Project Grants; Research Technics; Role; Self Administration; Serotonin; Sex Characteristics; Slice; Testing; Therapeutic; Toxic effect; United States; Universities; Utah; Work; Writing; addiction; base; career; density; drug of abuse; frontal lobe; immunoreactivity; improved; insight; interest; male; methamphetamine abuse; methamphetamine exposure; neurochemistry; optogenetics; public health relevance; receptor; serotonin transporter; skills

My overall career goal is to work in a university setting where I can pursue my research interests in the neurochemistry underlying addiction and relapse, potential interventions for addiction, and the behavioral consequences of addiction. The K99/R00 Pathways to Independence award is an important step in achieving this goal. The proposed award would allow me to achieve an independent career in academic research through mentoring, collaboration, research and new research skills, and grant writing. The University of Utah can provide the facilities and equipment, mentoring, and collaborative research environment to not only achieve the research proposed for the K99 award, but also launch my career as an independent investigator. The University of Utah has many prominent researchers in the field of methamphetamine (METH) toxicity that are committed to maximizing my potential as a researcher. My mentors, Dr. Fleckenstein and Hanson, have been instrumental in helping me achieve my postdoctoral career goal of enhancing my ability to study the neurochemical changes associated with drug addiction. The support provided by my mentors and mentoring committee (Drs. Bevins & Wilkins), and consultants (Drs. Yamamoto, LaLumiere, Keefe & Wilcox) will allow me to expand my research techniques by learning optogenetics and autoradiography, improve my grant writing and laboratory management skills, and enhance my abilities to teach and mentor future generations. The proposed research will allow me to expand beyond the scope of my mentors' research on the neurochemical effects METH self-administration (SA) in the striatum by investigating the role of neurochemical changes in the frontal cortex in METH SA and reinstatement. Since changes in the frontal cortex have been observed in human METH addicts and are implicated in the cognitive deficits associated with drug abuse, better understanding these changes are important for understanding addiction and relapse. This will be assessed by 1.) identifying the specific serotonergic changes that occur in the frontal cortex following METH SA; 2.) investigating the role of excitatory activity in the medial prefrontal cortex during the reinstatement of METH- seeking; 3.) investigating the role of serotonin and glutamate release and 5HT2A receptor stimulation in the medial prefrontal cortex during the reinstatement of METH-seeking; and 4.) investigating if sex differences in serotonergic function contribute to sex differences in METH-seeking. The current proposal will provide insight into the role of changes in the frontal cortex in the relapse of METH addiction and allow for the targeted development of potential therapeutics. It will also set the foundation to further investigate sex differences in drug abuse. In addition to conducting this important research, this grant will help enable me to submit an R03 grant to pilot data of the behavioral effects of the neurochemical changes following METH SA and R01 grant based on the findings of the proposed studies. The research proposed, in addition to the mentoring described, will enhance my potential to become a successful independent researcher investigating drug addiction.

我的总体职业目标是在大学工作，在那里我可以追求我的研究兴趣， 成瘾和复吸的神经化学基础，成瘾的潜在干预措施，以及行为 成瘾的后果。K99/R 00独立之路奖是实现 这个目标拟议中的奖项将使我能够在学术研究中实现独立的职业生涯 通过指导，合作，研究和新的研究技能，和赠款写作。犹他州大学 可以提供设施和设备，指导和协作研究环境，不仅 完成了K99奖的研究，也开始了我作为独立研究者的职业生涯。 犹他州大学在甲基苯丙胺（METH）毒性领域有许多杰出的研究人员， 致力于最大限度地发挥我作为研究人员的潜力。我的导师，弗莱肯斯坦博士和汉森， 帮助我实现了我的博士后职业目标，提高了我的研究能力， 与药物成瘾有关的神经化学变化。我的导师和指导提供的支持 委员会（Bevins & Wilkins博士）和顾问（Yamamoto，LaLumiere，Keefe & Wilcox博士）将允许我 通过学习光遗传学和放射自显影术来扩展我的研究技术，提高我的拨款写作 和实验室管理技能，并提高我的能力，教导和指导后代。的 我提出的研究将使我能够扩展我的导师对神经化学物质的研究范围 通过研究纹状体中神经化学变化的作用， METH SA中的额叶皮质和恢复。由于额叶皮层的变化已经被观察到， 人类METH成瘾者，并与药物滥用相关的认知缺陷有关， 理解这些变化对于理解成瘾和复发是很重要的。这将由 1.）的人。鉴定METH SA后额叶皮质中发生的特异性多巴胺能变化; 2.） 研究METH恢复过程中内侧前额叶皮层兴奋性活动的作用- 寻找; 3.研究5-羟色胺和谷氨酸的释放和5 HT 2A受体刺激在脑缺血中的作用。 恢复寻求甲基苯丙胺期间的内侧前额叶皮质;和4.）调查是否存在性别差异 促肾上腺皮质激素能功能有助于在寻求甲基苯丙胺的性别差异。目前的建议将提供深入了解 在METH成瘾复发的额叶皮层的变化的作用，并允许有针对性的 开发潜在的治疗方法。这也将为进一步研究性别差异奠定基础。 吸毒除了进行这项重要的研究，这笔赠款将帮助我提交一份R 03 授予METH SA和R 01授予后神经化学变化的行为影响的飞行员数据 根据拟议研究的结果。这项研究提出，除了所描述的指导， 将增强我成为一名成功的独立研究人员调查吸毒成瘾的潜力。