Pharmacology and Toxicology of Methamphetamine Abuse (K05 DA00378)

描述（由申请人提供）：这是一个有竞争力的格伦汉森博士的高级科学家奖续期申请。汉森博士是药理学系的终身教授。& Tox。在犹他州大学，拥有20多年的药物滥用研究经验，为我们理解精神兴奋剂对大脑单胺能和神经肽系统的短期和长期影响做出了重要贡献。汉森博士的K 05奖（始于1998年）使他从繁重的教学和委员会责任中解脱出来，使汉森博士能够将超过75%的专业时间投入到与药物滥用/成瘾研究相关的工作中。他的K 05奖支持的活动产生了：（i）约57篇同行评审的科学出版物;（ii）在科学会议上提交了90多篇摘要;（iii）被任命为NIDA神经科学和行为研究部主任（2000-2001年）; ㈣成为国家药物滥用研究所代理所长（2001-2003年）;（v）被任命为犹他州成瘾中心主任（2003年至今）;（vi）成为NIDA主任的高级顾问（2003年至今）。更新Hanson博士的K 05将使他能够指导研究以测试以下主要假设：（i）纹状体-黑质途径的功能输出通过给予低剂量的甲氨喋呤而增加，并且不受给予高剂量该药物的影响;（ii）囊泡单胺转运蛋白-2的急性反应的第二组分而不是第一组分的表达与苯乙胺诱导的单胺神经毒性的发生有关;和（iii）在青少年、先前受损和耐受大鼠中，黑质纹状体多巴胺通路对甲基苯丙胺诱导的神经毒性的不应性存在相关的基本机制。继续他的K 05将使Hanson博士能够发展技术方面的专业知识，这些技术将大大促进他的研究工作，例如：（i）亚细胞分级分离;（ii）蛋白质印迹和免疫沉淀蛋白质表征;（iii）旋转圆盘电极伏安法;和（iv）自我管理应急范例。除了研究项目外，K 05的支持将使Hanson博士能够直接努力创建跨学科研究团队，进行药物滥用和转化研究。最后，该奖项将允许汉森博士继续指导本科生，研究生，博士后和年轻教师级别的经验不足的研究人员，以帮助他们的科学发展。

DESCRIPTION (provided by applicant): This is a competitive renewal application for Dr. Glen Hanson's Senior Scientist Award. Dr. Hanson is a tenured professor in the Department of Pharmacol. & Tox. at the University of Utah with more than 20 years experience in drug abuse research resulting in important contributions to our understanding of the short- and long-term effects of psychostimulants on brain monoaminergic and neuropeptide systems. Dr. Hanson's K05 award (beginning in 1998) has relieved him from heavy teaching and committee responsibilities, allowing Dr. Hanson to devote > 75% of his professional time to substance abuse/addiction research-related endeavors. Activities supported by his K05 award resulted in: (i) ~57 peer-reviewed scientific publications; (ii) >90 abstracts presented at scientific meetings; (iii) an appointment as the director of NIDA's Division of Neuro-science and Behavioral Research (2000-2001); (iv) becoming the acting Director of the National Institute on Drug Abuse (2001-2003); (v) an appointment as the director of the Utah Addiction Center (2003-present); and (vi) becoming a senior advisor to the director of NIDA (2003-present). Renewal of Dr. Hanson's K05 will permit him to direct research to test the following principal hypotheses: (i) the functional output of the striato-nigral pathway is increased by administration of low doses of methamphtamine and unaffected by administration of high doses of this drug; (ii) expression of a 2nd , but not the 1st , component of an acute response of the vesicular monoamine transporter-2 is linked to the occurrence of phenylethylamine-induced monamine neurotoxicity; and (iii) there are related mechanisms fundamental to the refractoriness of the nigrostriatal dopamine pathway to methamphetamine-induced neurotoxicity in: adolescent; previously lesioned; and tolerant, rats. Continuation of his K05 will allow Dr. Hanson to develop expertise in technologies that will substantially further his research efforts, such as: (i) subcellular fractionation; (ii) Western blotting and immunoprecipitation protein characterization; (iii) rotating disk electrode voltammetry; and (iv) self-administration contingency paradigms. In addition to research projects, the K05 support will allow Dr. Hanson to direct efforts to create interdisciplinary research teams to conduct drug abuse and translational research. Finally, this award will permit Dr. Hanson to continue mentoring inexperienced researchers at the under-graduate, graduate, postdoctoral and young faculty levels, to assist them in their scientific development.