Cannabinoid Modulation of Cell Function

描述（由申请人提供）：这是一份更新高级科学家研究和指导奖的申请，为Ken Mackie提供受保护的时间，以便他可以在研究，指导和职业发展方面实现以下目标。未来五年的具体研究目标包括：(1)全面了解CB1大麻素受体脱敏的机制；(2)识别内源性和外源性大麻素在胚胎期和青春期前额叶皮层成熟两个关键神经发育阶段的作用；(3)探索CB2大麻素受体功能选择性在制造更有效镇痛药和减轻可卡因奖励方面的治疗潜力。(4)利用简化的实验系统（主要是培养的自适应神经元）来解决内源性大麻素介导的突触可塑性中重要的、突出的问题。麦基博士的指导将侧重于指导四组科学家，他们涵盖了整个职业范围：印第安纳大学的本科生、印第安纳大学的研究生和医学院学生、博士后研究员和初级教员。他的职业发展将强调将更强大的成像、信息学、蛋白质组学和行为学工具整合到他的研究中，并继续致力于与药物滥用研究相关的服务（编辑职责、会议组织和拨款审查）。

DESCRIPTION (provided by applicant): This is an application for the renewal of a senior scientist research and mentorship award to provide protected time for Ken Mackie so he can achieve the following goals for his research, mentoring, and career development. Specific research objectives during the next five years include: (1) Obtaining a comprehensive understanding of the mechanisms of CB1 cannabinoid receptor desensitization, (2) Discerning the roles of endogenous and exogenous cannabinoids during two key neurodevelopmental stages (A) during embryonic life and (B) during the adolescent maturation of the prefrontal cortex, (3) Exploring the therapeutic potential of CB2 cannabinoid receptor functional selectivity in making more effective analgesics and in attenuating cocaine reward, (4) Using simplified experimental systems (primarily cultured autaptic neurons) to address significant, outstanding issues in endocannabinoid-mediated synaptic plasticity. Dr. Mackie's mentoring will focus on mentoring four groups of scientists that encompass the full career spectrum: undergraduates at Indiana University, graduate and medical students at Indiana University, post-doctoral fellows, and junior faculty. His career development will emphasize the incorporation of more powerful imaging, informatic, proteomic, and behavioral tools into his research, as well as continuing to be heavily committed to service (editorial duties, meeting organization, and grant reviews) related to drug abuse research.