Cannabinoid Modulation of Cell Function

描述（由申请人提供）：这是一个高级科学家研究和指导奖的续期申请，为肯·麦基提供受保护的时间，使他能够实现他的研究，指导和职业发展的以下目标。未来五年的具体研究目标包括：（1）获得对CB 1大麻素受体脱敏机制的全面理解，（2）辨别内源性和外源性大麻素在两个关键神经发育阶段（A）胚胎生命期间和（B）前额叶皮质青春期成熟期间的作用，（3）探索CB2大麻素受体功能选择性在制备更有效的镇痛剂和减弱可卡因奖赏中的治疗潜力，（4）使用简化的实验系统（主要培养自适应神经元）来解决内源性大麻素介导的突触可塑性中的重大、悬而未决的问题。Mackie博士的指导将侧重于指导四组科学家，包括整个职业范围：印第安纳州大学的本科生，印第安纳州大学的研究生和医学生，博士后研究员和初级教师。他的职业发展将强调将更强大的成像，信息学，蛋白质组学和行为工具纳入他的研究，以及继续致力于与药物滥用研究相关的服务（编辑职责，会议组织和资助审查）。

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.